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S001448862030087X | Spinal interneurons which discharge in phase with the respiratory cycle have been repeatedly described over the last 50years . These spinal respiratory interneurons are part of a complex propriospinal network that is synaptically coupled with respiratory motoneurons . This article summarizes current knowledge regarding spinal respiratory interneurons and emphasizes chemical electrical and physiological methods for activating spinal respiratory neural circuits . Collectively the work reviewed here shows that activating spinal interneurons can have a powerful impact on spinal respiratory motor output and can even drive rhythmic bursting in respiratory motoneuron pools under certain conditions . We propose that the primary functions of spinal respiratory neurons include 1 shaping the respiratory pattern into the final efferent motor output from the spinal respiratory nerves 2 coordinating respiratory muscle activation across the spinal neuraxis 3 coordinating postural locomotor and respiratory movements and 4 enabling plasticity of respiratory motor output in health and disease . | Spinal interneurons INs with respiratory discharge patterns are well described. Spinal respiratory motoneurons are synaptically coupled to spinal INs. Spinal INs can modulate respiratory motoneuron activity. Chemical electrical and physiological methods can activate spinal respiratory INs. Targeted activation of spinal INs may restore breathing after spinal cord injury. |
S0014488620300893 | Spinal cord injury induces a secondary degenerative response that causes the loss of spared axons and worsens neurological outcome . The complex molecular mechanisms that mediate secondary axonal degeneration remain poorly understood . To further our understanding of secondary axonal degeneration following SCI we assessed the spatiotemporal dynamics of axonal spheroid and terminal bulb formation following a contusive SCI in real time in vivo . Adult 68week old | Intravital imaging following contusive SCI reveals changes in spinal axons in real time. Axons predominantly undergo spheroid formation acutely after contusive SCI. Axonal spheroids spread mediolaterally over time indicative of secondary injury. Axonal spheroids are highly dynamic and can resolve spontaneously. Disrupted axonal transport likely underlies spheroid and endbulb formation. |
S0014488620300923 | Cerebral small vessel disease is a common condition linked to dementia and stroke . As an age dependent brain pathology cerebral SVD may share molecular processes with core neurodegenerative diseases such as Alzheimer s and Parkinson s disease . Many neurodegenerative diseases feature abnormal protein accumulation and aberrant protein folding resulting in multimerization of specific proteins . We investigated if a small NOTCH3 N terminal fragment that co registers with pathologically affected cells in the inherited SVD CADASIL is capable of multimerization . We also characterized endogenous small molecule vascular enhancers and inhibitors of multimerization . NTF multimerizes spontaneously and also forms conjugates with vascular catecholamines including dopamine and norepinephrine which avidly promote multimerization of the protein . Inhibition of catecholamine dependent multimerization by vitamin C and reversal by reducing agents implicate an essential role of oxidation in NTF multimerization . Antibodies that react with degenerating arteries in CADASIL tissue preferentially bind to multimerized forms of NTF . These studies suggest that multimerization of proteins in the aging brain is not restricted to neuronal molecules and may participate in age dependent vascular pathology . | A NOTCH3 protein cleavage product N terminal fragment NTF undergoes spontaneous cysteine mediated multimerization. Catecholamines interact with NOTCH3 facilitating protein multimerization. Catechol like components are incorporated into NTF multimers. Inhibitors and reversal agents of NTF multimerization include anti oxidants and reducing agents |
S0014488620300959 | Status epilepticus is a state of prolonged and repeated seizures that can lead to permanent brain damage or life threatening conditions . Transcranial direct current stimulation non invasively provides a polarity specific electric current to modulate brain excitability . Little is known about the therapeutic potential of tDCS in SE . Here we aim to determine the tDCS effects on seizure severity EEG and post SE consequences in rats with kainic acid induced SE . Rats were subjected to cathodal tDCS or sham stimulation over the dorsal hippocampus for 5days . KA was intraperitoneally injected to induce SE . We used continuous video EEG recording to monitor seizure activity immunostaining and Timm staining to evaluate neuron counts and mossy fiber sprouting and ELISA for Brain derived neurotrophic factor protein measurement . Two featured EEG patterns gamma ranged high frequency polyspikes and low frequency spike and wave complexes were identified in the hippocampal CA1 of KA induced SE rats . tDCS elicited a significant decrease in severe seizures of Racine stages 45 in KA induced SE rats . tDCS treated rats manifested diminished high frequency oscillation during SE decreased chronic spontaneous spike activities and mossy fiber sproutings compared to sham . tDCS treated rats also exhibited significantly lower hippocampal BDNF protein levels than sham immediately and 4weeks after SE . A positive correlation between the hippocampal BDNF level and the seizure severity of SE was found . Altogether our results show that repeated cathodal tDCS can mitigate seizure severity alter ictal EEG pattern and reduce the chronic adverse consequences in KA induced SE rats supporting the therapeutic potential of tDCS in severe prolonged epileptic seizures . | Repeated cathodal tDCS reduces seizure severity in status epilepticus rat model. TDCS decreases the gamma ranged high frequency oscillation polyspikes on ictal EEG. Less chronic spontaneous spikes are observed in tDCS treated rats. Decreased BDNF expression correlates with less seizure severity in tDCS treated rats. |
S0014488620301047 | This report was produced by an Expert Working Group consisting of UK based researchers veterinarians and regulators of animal experiments with specialist knowledge of the use of animal models of spinal cord injury . It aims to facilitate the implementation of the Three Rs with an emphasis on refinement . Specific animal welfare issues were identified and discussed and practical measures proposed with the aim of reducing animal use and suffering reducing experimental variability and increasing translatability within this critically important research field . | Pre clinical research into SCI is currently dominated by the use of animal models. These models can involve significant injury and have the potential to cause high levels of suffering. A UK based expert working group has identified animal welfare issues associated with modelling SCI in animals. This article sets out practical refinements to improve animal welfare. |
S0014488620301114 | Medial temporal lobe epilepsy is among the most common and most drug resistant types of epilepsies associated with remodeling of the trisynaptic circuit of the hippocampus . The cornu ammonis 3 region as the pacemaker of the circuit and CA3CA1 synapse are potential targets for suppression of MTLE . We examined optogenetic manipulation of CA3 neurons in controlling the perforant pathway kindled seizures . One week after implantation of stimulating electrodes in perforant pathway a recording electrode in CA1 and an optic fiber in CA3 rats underwent rapid kindling procedure . A lentivector with capability to move in retrograde monosynaptic direction and to insert the gene of red light sensitive opsin | The light sensitive chloride pump. was encoded in CA1 CA3 and entorhinal cortex of rats. Rats expressing. became epileptic by electrical kindling of perforant pathway. Light Illumination to CA3 of the kindled rats expressing. suppressed seizures. |
S0014488620301126 | Charcot Marie Tooth type 2A peripheral neuropathy the most common axonal form of CMT is caused by dominantly inherited point mutations in the Mitofusin 2 | CMT2A. mice show early onset of neuropathic pain and progressive motor performance defects. CMT2A. mice exhibit a progressive decrease of tubulin acetylation in distal sciatic nerves. Treatment of CMT2A. mice with an HDAC6 inhibitor SW 100 rescues distal sciatic nerves tubulin acetylation. SW 100 ameliorates CMT2A. mouse motor and sensory defects when given prior to or after the onset of symptoms. HDAC6 genetic deletion in CMT2A. mice prevents their development of motor performance defects and neuropathic pain. HDAC6 is a promising therapeutic target for CMT2A |
S001448862030114X | It has been proposed that Amyloid Precursor Protein might act as a rheostat controlling neuronal excitability but mechanisms have remained untested . APP and its catabolite A are known to impact upon synapse function and dysfunction via their interaction with the prion protein PrP | Zebrafish lacking amyloid precursor protein APP are susceptible to seizures. Zebrafish lacking prion protein are sensitized to acute loss of APP. Mammalian prion protein can replace its zebrafish homolog during APP interaction. Seizure susceptibility of APP mutants requires intact prion protein. Seizure susceptibility of prion mutant fish involves mGluR5 channels and APP. |
S0014488620301151 | Parkinson s disease is a major neurodegenerative disorder characterized by a variety of non motor symptoms in addition to the well recognized motor dysfunctions that have commanded primary interest . We previously described a new PD mouse model based on heterozygous disruption of the | New mouse model of PD based on GM1 deficiency shows non movement and movement disorders. Non movement disorders include lesions in colon and heart short term memory loss. GM1 deficient mice showed symptoms of constipation characteristic of prodromal PD. E.coli synthesized GM1 was shown to be effective in remedying all PD lesions. |
S0014488620301187 | The antiarrhythmic sodium channel blocker mexiletine is used to treat patients with myotonia . However around 30 of patients do not benefit from mexiletine due to poor tolerability or suboptimal response . Safinamide is an add on therapy to levodopa for Parkinson s disease . In addition to MAOB inhibition safinamide inhibits neuronal sodium channels conferring anticonvulsant activity in models of epilepsy . Here we investigated the effects of safinamide on skeletal muscle hNa | Safinamide reversibly inhibits skeletal muscle voltage gated sodium channels. Safinamide effects on sodium channels are voltage and frequency dependent. Safinamide likely binds to the local anesthetic receptor in the sodium channel pore. Safinamide reduces action potential firing in hyperexcited rat skeletal muscle fibers. Safinamide counteracts muscle stiffness in the myotonic rat in vivo. |
S0014488620301205 | Decreases in energy metabolism following traumatic brain injury are attributed to impairment of glycolytic flux and oxidative phosphorylation . Glucose utilization post TBI is decreased while administration of alternative substrates has been shown to be neuroprotective . Changes in energy metabolism following TBI happens in two phases a period of hyper metabolism followed by prolonged hypo metabolism . It is not understood how different cerebral metabolic states may impact substrate metabolism and ultimately mitochondrial function . Adult male or female Sprague Dawley rats were given sham surgery or controlled cortical impact and were assigned one of two administration schemes . Glucose lactate or beta hydroxybutyrate were infused i.v . either starting immediately after injury or beginning 6h post injury for 3h to reflect the hyper and hypo metabolic stages . Animals were euthanized 24h post injury . The peri contusional cortex was collected and assayed for mitochondrial respiration peroxide production and citrate synthase activity . Tissue acetyl CoA ATP glycogen and HMGB1 were also quantified . Sex differences were observed in injury pattern . Administration based on cerebral metabolic state identified that only early lactate and late BHB improved mitochondrial function and peroxide production and TCA cycle intermediates in males . In contrast both early and late BHB had deleterious effects on all aspects of metabolic measurements in females . These data stress there is no one optimal alternative substrate but rather the fuel type used should be guided by both cerebral metabolic state and sex . | Alternative substrates were given during hyper or hypo cerebral metabolic states. Alternative substrate metabolism was dependent on cerebral metabolic state. Optimal substrate delivery was determined by mitochondrial outcomes. Metabolic injury patterns were sex dependent. Sex differences were observed in substrate metabolism. |
S0014488620301217 | Modeling experimental traumatic brain injury in rodents is necessarily required to understand the pathophysiological and neurobehavioral consequences of neurotrauma . Numerous models have been developed to study experimental TBI . Fluid percussion injury is the most extensively used model to represent clinical phenotypes . Nevertheless the surgical sham procedure a prerequisite of FPI is the impeding factor in experimental TBI . We hypothesized that if craniectomy causes substantial structural and functional changes in the brain it might mimic the mild FPI induced neurobehavioral dysfunctions . To understand the hypothesis C57BL 6 mice were exposed to lateral FPI at 1.2atm pressure and changes in the neuronal architecture hippocampal neurogenesis neuroinflammation and behavioral functions were compared to the sham and control mice at day 7 post FPI . We observed that both the craniectomy and FPI significantly augmented the ipsilateral hippocampal neurogenesis as evaluated by DCX and Beta III tubulin immunoreactivity . Similarly a significant increase in GFAP and TMEM immunoreactivity in CA1 and CA3 regions showed that craniectomy mimics FPI induced neuroinflammation . The additive damaging effect of craniectomy with FPI was also reported in the term of axonal and dendritic fragmentation swelling and neuronal death using silver staining Fluoro jade and MAP 2 immunoreactivity . Sham exposed mice showed a significant functional decrease in grip strength . Our results indicate that sham craniectomy itself is enough to cause TBI like characteristics and thus fluid percussion at mild pressure is minimally additive with craniectomy . Considering the method as a mixed injury model the net neurotrauma severity should be compared with nave control instead of the sham as it is an outcome of cumulative damage due to fluid pressure and craniectomy . Nevertheless to understand the long term consequences of neurotrauma the extent of recovery in surgical sham may separately be quantified . | Low pressure fluid percussion minimally adds to craniectomyinduced neurotrauma. Craniectomy mimics mild fluid percussion induced neurotrauma. Both the craniectomy and fluid percussion augment neurogenesis at the early stage. Craniectomy is additively damaging with FPI in term of neurobehavioral changes. Craniectomy causes locomotor hyperactivity and neuroinflammation. |
S0014488620301321 | The goal of this study in anesthetized cats was to identify silent hypogastric nerve afferent fibers that do not respond to bladder distention but become responsive after chemical irritation of the bladder . The HGN was split into multiple filaments small enough for recording action potentials from single or multiple afferent fibers . The bladder was distended by infusion of either saline or 0.5 acetic acid through a urethral catheter while recording intravesical pressure . A total of 90 HGN filaments from 17 cats responded to bladder distention with saline or AA . Three types of HGN afferents were identified . The first type was non nociceptive mechano sensitive that responded to bladder distention at normal physiological pressures 1040 cmH | Hypogastric afferents respond to both bladder distention and irritation. Silent hypogastric afferents can only respond to high bladder pressure. Some chemo sensitive hypogastric afferents do not respond to bladder distension. Hypogastric afferents may play an important role in bladder pain or overactivity. |
S0014488620301345 | Death associated protein kinase 1 is a key protein that mediates neuronal death in ischemic stroke . Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered the modulation of DAPK1 itself is still unclear . Here we first reveal that Caytaxin a brain specific member of BCL2 adenovirus E1B interacting protein increases and interacts with DAPK1 as early as 2h after middle cerebral artery occlusion in the penumbra area of mouse brain . Furthermore Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity . Silencing Caytaxin by Caytaxin shRNA enhances DAPK1 activity deteriorates neuronal apoptosis and brain injuries both | Caytaxin increases in the ischemic brain at the early phase of cerebral ischemic stroke. Caytaxin interacts and inhibits DAPK1 in the presynaptic area. Caytaxin prevents neuronal apoptosis and alleviates ischemic brain injury by inhibiting DAPK1 catalytic activity. |
S0014488620301370 | Reduction of conditioned fear expression by extinction underlies cue exposure therapies that treat anxiety disorders . Extinction is context specific . Renewal for example is the relapse of extinguished fear when subjects are tested in a different context to extinction . This context specificity is developmentally regulated and sex dependent with renewal being observed in postnatal day 18 female but not in male rats . Given the hippocampus is critical for context specific extinction in adult rodents we investigated dorsal or ventral hippocampus involvement in context specific extinction in P18 male and female rats . We microinfused muscimol GABA | Inactivation of dorsal hippocampus accelerated extinction in juvenile rats. Inactivation of ventral hippocampus impaired extinction recall in juvenile rats. Renewal of extinguished fear was observed in juvenile females but not males. Hippocampus inactivation did not affect sex differences in renewal. |
S0014488620301394 | Stroke remains a leading cause of disability in the United States . Despite recent advances interventions to reduce damage and enhance recovery after stroke are lacking . P2X4R a receptor for adenosine triphosphate regulates activation of myeloid immune cells after stroke injury . However over stimulation of P2X4Rs due to excessive ATP release from dying or damaged neuronal cells can contribute to ischemic injury . Therefore we pharmacologically inhibited P2X4R to limit the over stimulated myeloid cell immune response and improve both acute and chronic stroke recovery . We subjected 812 week old male and female wild type mice to a 60min right middle cerebral artery occlusion followed by 3 or 30days of reperfusion . We performed histological RNA sequencing behavioral and biochemical analyses to determine the acute and chronic effects of P2X4R antagonist 5 BDBD treatment . 5 BDBD treatment significantly reduced infarct volume neurological deficit score levels of cytokine interleukin 1 beta and blood brain barrier permeability in the 3 day group . Chronically 5 BDBD treatment also conferred progressive recovery of motor balance and coordination using a rotarod test as well as reduced anxiety like behavior over 30days . Interestingly depressive type behavior was not observed in mice treated with 5 BDBD for 3days . In addition flow cytometric analysis revealed that 5 BDBD treatment decreased the total number of infiltrated leukocytes and among those infiltrated leukocytes pro inflammatory cells of myeloid origin were specifically reduced . 5 BDBD treatment reduced the cell surface expression of P2X4R in flow cytometry sorted monocytes and microglia without reducing the total P2X4R level in brain tissue . In summary acute P2X4R inhibition protects against ischemic injury at both acute and chronic time points after stroke . Reduced numbers of infiltrating pro inflammatory myeloid cells decreased surface P2X4R expression and reduced BBB disruption are likely its mechanism of neuroprotection and neuro rehabilitation . | Acute blockade of P2X4R provide neuroprotection and neuro rehabilitation. 5 BDBD reduce infiltration of peripheral immune cells after stroke. 5 BDBD treatment diminish BBB permeability and myeloid cell activation. |
S0014488620301436 | Fluoxetine is one of the most promising drugs for improving clinical outcome in patients with ischemic stroke . This in vivo study investigated the hypothesis that fluoxetine may affect HIF 1 Netrin VEGF cascade angiogenesis and neuroprotection using a rat model of transient middle cerebral artery occlusion . The rats were given fluoxetine or saline after tMCAO for 4weeks . Then protein expression of HIF 1 Netrin VEGF cascade was examined at 1 2 4weeks after tMCAO . In vivo synchrotron radiation were performed to observe microangiography of ischemic brain after 4weeks of tMCAO . The infarct size and neurobehavioral test were carried out 1 to 4weeks after tMCAO . Results revealed that HIF 1 expression was upregulated in fluoxetine treated group . Similarly fluoxetine increased protein expression of Netrin and its receptor DCC VEGF and its receptor VEGFR . Synchrotron radiation angiography revealed more branches in fluoxetine treated rats . We found no difference of infarct volume between fluoxetine and saline treated rats after 1week of tMCAO and ischemia induced brain atrophy volume in fluoxetine treated group was attenuated after 4weeks of tMCAO . Neurological deficits were improved in fluoxetine treated rats at 3 and 4weeks after tMCAO . Our results indicated that fluoxetine could upregulate protein expression of HIF 1 Netrin VEGF cascade promote angiogenesis and improve long term functional recovery after ischemic stroke . | Fluoxetine upregulates HIF 1 Netrin VEGF cascade. Fluoxetine promotes neovascularization in cerebral ischemic conditions. |
S001448862030145X | Despite internationally established diagnostic criteria multiple system atrophy is frequently misdiagnosed particularly at disease onset . While neuropathological changes such as demyelination and iron deposition are typically detected in MSA these structural hallmarks were so far only demonstrated | MBP29 h syn mice show severe myelin deficit and iron accumulation in white matter. Quantitative susceptibility mapping QSM visualizes and quantifies both hallmarks. QSM and T2 weighted MRI allow precise distinction of MBP29 h syn mice from controls. Magnetic susceptibility highly correlated with iron and myelin optical density. |
S0014488620301461 | Parkinson s disease a debilitating progressive degenerative movement disorder associated with loss of dopaminergic neurons in the substantia nigra afflicts approximately one million people in the U.S. including a significant number of Veterans . Disease characteristics include tremor rigidity postural instability bradykinesia and at a cellular level glial cell activation and Lewy body inclusions in DA neurons . The most potent medical surgical treatments do not ultimately prevent disease progression . Therefore new therapies must be developed to halt progression of the disease . While the mechanisms of the degenerative process in PD remain elusive chronic inflammation a common factor in many neurodegenerative diseases has been implicated with associated accumulation of toxic aggregated synuclein in neurons . Calpain a calcium activated cysteine neutral protease plays a pivotal role in SN and spinal cord degeneration in PD via its role in synuclein aggregation activation migration of microglia and T cells and upregulation of inflammatory processes . Here we report an increased expression of a subset of CD4 T cells in rodent models of PD including MPTP mice and DSP 4 N ethyl 2 bromobenzylamine hydrochloride 6 hydroxydopamine rats which produced higher levels of perforin and granzyme B typically found in cytotoxic T cells . Importantly the CD4 cytotoxic subtype was attenuated following calpain inhibition in MPTP mice suggesting that calpain and this distinct CD4 T cell subset may have critical roles in the inflammatory process disease progression and neurodegeneration in PD . | Calcium activated neutral protease calpain plays a role in T cell activation. A subset of CD4 T cells was upregulated in rat and mouse models of PD. The CD4 cytotoxic T cell subtype was attenuated with calpain inhibition. |
S0014488620301473 | The development and translation of cell therapies have been hindered by an inability to predict and evaluate their efficacy after transplantation . Using an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis we studied attenuation of the diffuse injury characteristic of EAE and MS by transplanted glial restricted precursor cells . We assessed the potential of on resonance variable delay multiple pulse chemical exchange saturation transfer MRI to visualize this attenuation . Allogeneic GRPs transplanted in the motor cortex or lateral ventricles attenuated paralysis in EAE mice and attenuated differences compared to nave mice in onVDMP CEST signal 5days after transplantation near the transplantation site . Histological analysis revealed that transplanted GRPs co localized with attenuated astrogliosis . Hence diffuse injury sensitive onVDMP CEST MRI may complement conventional MRI to locate and monitor tissue regions responsive to GRP therapy . | onVDMP CEST MRI signal changes in the brain as paralysis progresses. Stem cell transplantation in the motor cortex attenuates paralysis. onVDMP CEST MRI locates brain regions responsive to transplanted cell therapy |
S0014488620301485 | Neonatal hypoxia ischemia is the main cause of newborn mortality and morbidity . Preclinical studies have shown that the immature rat brain is more resilient to HI injury suggesting innate mechanisms of neuroprotection . During neonatal period brain metabolism experience changes that might greatly affect the outcome of HI injury . Therefore the aim of the present study was to investigate how changes in brain metabolism interfere with HI outcome in different stages of CNS development . For this purpose animals were divided into 6 groups HIP3 HIP7 and HIP11 and their respective shams . | HI injury has different prognosis depending on the age it is induced. While P3 brain is more resilient the P11 brain is greatly affected. Higher usage of BHB instead of glucose is a possible mechanism of P3 resiliency. |
S0014488620301497 | Early life stress is a risk factor for many psychopathologies that happen later in life . Although stress can occur in cases of child abuse studies on non accidental brain injuries in pediatric populations do not consider the possible increase in vulnerability caused by ELS . Hence we sought to determine whether ELS increases the effects of pediatric mild traumatic brain injury on cognition hippocampal inflammation and plasticity . Male rats were subjected to maternal separation for 180min per day or used as controls during the first 21 post natal days . At P21 the rats were anesthetized with isoflurane and subjected to a mild controlled cortical impact or sham injury . At P32 the rats were injected with the cell proliferation marker bromodeoxyuridine then evaluated for spatial learning and memory in a water maze and sacrificed for quantification of Ki67 | Early life stress ELS increases cognitive impairments after mild pediatric TBI. ELS increases hippocampal microglial activation after mild pediatric TBI. ELS TBI decreases proliferation in the hippocampal neurogenic niche. ELS TBI did not further affect the survival or differentiation of newly generated cells. |
S0014488620301515 | Blood brain barrier hyperpermeability and brain edema contribute to increased seizure susceptibility and brain injury in status epilepticus . The endothelial glycocalyx is the coating on luminal side of the endothelium and can be considered as the first barrier of BBB . Currently little is known about the effects of endothelial glycocalyx in SE . We hypothesized glycocalyx degradation could be considered as a first step in the pathophysiology of SE . The study aimed to investigate the impacts of glycocalyx integrity loss on brain damage in a C57BL 6 mouse model of SE induced by lithium pilocarpine and whether heparin a competitive antagonist against heparinase improves survival and neurological outcome . Compared to controls glycocalyx was significantly degraded after SE which was mitigated by heparin . The glycocalyx disruption was associated with higher BBB permeability and aggravated brain edema at 72h after SE as well as lower survival rate and poorer neurologic outcome . Conversely preservation of glycocalyx by heparin could reduce SE induced activation of glia cells BBB leakage brain edema decrease the expressions of inflammatory factors and improve neurologic outcome . The study highlights the importance of glycocalyx degradation in cerebral edema and SE outcome and indicates heparin treatment may be a new strategy for brain protection in SE . | Glycocalyx degradation may be the first step in the pathogenesis of SE. Heparin ameliorated the glycocalyx degradation in SE. Preservation of glycocalyx by heparin reduce SE induced injury and improve outcome. Heparin ameliorated BBB disruption and cerebral edema in SE. Heparin treatment may be a new strategy for brain protection in SE. |
S0014488620301539 | Traumatic brain injury results in mitochondrial dysfunction and induction of lipid peroxidation . Lipid peroxidation derived neurotoxic aldehydes such as 4 HNE and acrolein bind to mitochondrial proteins inducing additional oxidative damage and further exacerbating mitochondrial dysfunction and LP . Mitochondria are heterogeneous consisting of both synaptic and non synaptic populations with synaptic mitochondria being more vulnerable to injury dependent consequences . The goal of these studies was to explore the hypothesis that interrupting secondary oxidative damage following TBI using phenelzine an aldehyde scavenger would preferentially protect synaptic mitochondria against LP mediated damage in a dose and time dependent manner . Male Sprague Dawley rats received a severe controlled cortical impact TBI . PZ was administered subcutaneously at different times post injury . We found PZ treatment preserves both synaptic and non synaptic mitochondrial bioenergetics at 24h and that this protection is partially maintained out to 72h post injury using various dosing regimens . The results from these studies indicate that the therapeutic window for the first dose of PZ is likely within the first hour after injury and the window for administration of the second dose seems to fall between 12 and 24h . Administration of PZ was able to significantly improve mitochondrial respiration compared to vehicle treated animals across various states of respiration for both the non synaptic and synaptic mitochondria . The synaptic mitochondria appear to respond more robustly to PZ treatment than the non synaptic and further experimentation will need to be done to further understand these effects in the context of TBI . | Phenelzine an effective pharmacological strategy against oxidative damage post TBI. PZ mediated protection against non synaptic and synaptic mitochondrial dysfunction. PZ protects against aldehyde mediated damage to non synaptic synaptic mitochondria. Importance of timing dosing for pharmacological neuro mito protective strategies |
S0014488620301552 | Neonatal hypoxic ischemic encephalopathy remains the most important neurological problem of the newborn . Delays in diagnosing perinatal brain injuries are common preventing access to acute therapies . Therefore there is a critical need for therapeutic strategies that are beneficial when delivered beyond 24h after birth . Here we show that Leukemia Inhibitory Factor functions as an essential injury induced neurotrophic cytokine in the CNS and that non invasively administering LIF as late as 3days after a hypoxic ischemic insult improves neurological function . Using a mouse model of late preterm brain injury we show that astroglial and microglial macrophage reactivity to hypoxia ischemia was diminished at 3days of recovery but then exacerbated at 2weeks of recovery in LIF haplodeficient mice . There also were significantly more CD68 Iba 1 cells in the ipsilateral striatum in LIF Het mice compared to WT mice at 2weeks of recovery . This desynchronized glial response was accompanied by increased neuronal cell death in the striatum and neocortex hypomyelination increased extent of brain damage and diminished neurological function on sensorimotor tests . To our surprise injured LIF Het mice had 7 fold higher IGF 1 levels than injured WT mice at 3days after H | Brain damage is exacerbated after perinatal hypoxia ischemia in LIF Haplodeficient mice. 1st demonstration of therapeutic efficacy of intranasally delivered LIF for a neurological disorder. Intranasal LIF penetrates deep into the brain to activate survival promoting Stat 3 signaling. Administering LIF intranaslally as late as 3days after injury prevents tertiary neurodegeneration. Delayed intranasal LIF improves sensorimotor recovery. |
S0014488620301564 | Exosomes are emerging as novel players in the beneficial effects induced by exercise on vascular diseases . We have recently revealed that moderate exercise enhances the function of circulating endothelial progenitor cell derived EXs on protecting endothelial cells against hypoxia injury . However the relationship between the changes of cEPC EXs and the effects of exercise on ischemic stroke is unknown . Here we investigated whether exercise regulated EPC EXs contribute to the beneficial effects of exercise on IS . C57BL 6 mice received moderate treadmill exercise for 4 wks and then were subjected to middle cerebral artery occlusion stroke . The neurologic deficit score infarct volume microvessel density cell apoptosis angiogenesis neurogenesis sensorimotor functions were determined on day 2 and or day 28 post stroke . The miR 126 and EPC EX levels were analyzed by RT PCR or nanoparticle tracking analysis combined with microbeads and used for correlation analyses . The function of EPC EXs from exercised mice was detected in a hypoxia neuron model . Cell apoptosis axon growth ability and gene expressions were measured . Our data showed that i On day 2 exercised mice had decreased NDS and infarct volume reduced cell apoptosis rate and cleaved cas 3 level and a higher microvessel density than those in control mice . The levels of EPC EXs in plasma and brain tissue were raised and positively correlated in exercised mice . Meanwhile the miR 126 level in cEPC EXs and in ischemic tissue were upregulated in exercised mice . The EPC EXs and their carried miR 126 levels negatively correlated with the infarct volume and cell apoptosis whereas positively correlated with microvessel density . In addition cEPC EXs from exercised mice elicited protective effects on neurons against hypoxia induced apoptosis and compromised axon growth ability which were blocked by miR 126 and PI3k inhibitors in vitro . ii On day 28 exercised mice had less infarct volume higher microvessel density angiogenesis neurogenesis and better sensorimotor functions . The levels of BDNF p TrkB TrkB and p Akt Akt were upregulated in the brain of exercised mice . These recovery indexes correlated with the levels of cEPC EXs and their miR 126 . In conclusion our data suggest that moderate exercise intervention has protective effects on the brain against MCAO induced ischemic injury in both acute and chronic stages which might via the release of miR 126 enriched EPC EXs . | Moderate treadmill exercise alleviated acute injury in IS. Moderate treadmill exercise promoted chronic functional recovery in IS. Moderate treadmill exercise enhanced the function of cEPC EXs. The levels of cEPC EXs and miR 126 correlated with the acute injury index of IS. The levels of cEPC EXs and miR 126 correlated with the chronic recovery index of IS. |
S0014488620301576 | Cerebral ischemia reperfusion after cardiac arrest induces mitochondrial dysfunction and the timely removal of damaged mitochondria by mitophagy is reported to protect against cerebral I R injury . Therapeutic hypothermia has become an important component of postresuscitation care for patients who return to spontaneous circulation after CA . Previous studies have shown that TH can activate mitophagy and can contribute a protective effect however the optimal rewarming rate and underlying mechanism of rewarming following TH remain largely unexplained . Here we investigated the effects of different rewarming rates and whether mitophagy is involved in rewarming . After 5min of asphyxial CA following 4h of cooling Sprague Dawley rats were randomized into the normothermia hypothermia slow rewarming and fast rewarming groups . The hypothermia group was kept cool until tissue harvest the rewarming duration for the slow rewarming group and fast rewarming group was 6h and 45min respectively . We found that slowly rewarmed rats had better survival at 72h than normothermic rats and fast rewarmed rats and higher neurological deficit scores in which the medians were 57.33 26 and 28.83 respectively . In addition we explored the underlying mechanism during this process and found that PINK1 Parkin mediated mitophagy was activated during hypothermia in the slow rewarming group but was inhibited in the fast rewarming group . Further inhibition of mitophagy in the slowly rewarmed rats resulted in severe apoptosis and decreased the mean NDS from 58.39 to 33.11 indicating the protective role of mitophagy . Moreover the fast rewarming group exhibited deficiencies in PINK1 expression and mitophagy activity and marked accumulation of reactive oxygen species . Overall our results highlighted a neuroprotective role of PINK1 Parkin mediated mitophagy during slow rewarming after hypothermia . | Slow rewarming improves outcomes and activates PINK1 Parkin mediated mitophagy. Mitophagy inhibition aggravates apoptosis and neuronal damage during slow rewarming. PINK1 and mitophagy deficiency are accompanied by increased ROS in fast rewarming. |
S0014488620301588 | Numerous genes and alterations in their expression have been identified as risk factors for developing levodopa induced dyskinesia . However our understanding of the complexities of molecular changes remains insufficient for development of | Identical dyskinesia severity during first ever vs chronic levodopa induces differential gene expression. Divergent responses of F344 and Lewis rats offer a novel model for understanding genetic modulators of dyskinesias. The currently accepted genotype to phenotype relationships of. is brought into question. Striatal Nurr1 may represent a novel anti dyskinesia target. |
S001448862030159X | In order to repair chronic nerve injuries the damaged nerve segments are resected and stumps are bridged by grafts . Autografts remain the gold standard but outcomes are typically poor even after long periods of recovery . In a recent study we described the use of a nerve lengthening device to gradually elongate the proximal stump of a transected nerve towards the distal stump enabling a tension free end to end repair . This approach showed significantly improved outcomes in comparison to autografts in repairing acutely injured nerves . In this study we compared the use of nerve lengthening end to end repair to isograft repair of chronically transected nerves in a rat model . Structural and functional regenerative outcomes following LETER were comparable to isograft based repair with no significant differences found in outcomes involving functional recovery or axon growth . These data demonstrate the feasibility of nerve lengthening as a viable graft free strategy for repairing chronically injured nerves . Not unexpectedly outcomes for chronic nerve injuries were less favorable in both groups compared to repair of acutely injured nerves . Nonetheless the findings provide insight into barriers to restoring function after chronic nerve injury through novel comprehensive characterization of a diverse set of neuromuscular outcomes . This analysis revealed key parameters predicting functional recovery . | Recovery outcomes were similar when comparing nerve repairs by graft or lengthening. Nerve lengthening after chronic injury is viable and avoids need to harvest graft. Chronic and acute nerve injuries have very different outcomes. |
S0014488620301606 | Traumatic brain injury in children younger than 4years old results in cognitive and psychosocial deficits in adolescence and adulthood . At 4weeks following closed head injury on postnatal day 11 male and female rats exhibited impairment in novel object recognition memory along with an increase in open arm time in the elevated plus maze suggestive of risk taking behaviors . This was accompanied by an increase in intrinsic excitability and frequency of spontaneous excitatory post synaptic currents and a decrease in the frequency of spontaneous inhibitory post synaptic currents in layer 2 3 neurons within the medial prefrontal cortex a region that is implicated in both object recognition and risk taking behaviors . Treatment with progesterone for the first week after brain injury improved NOR memory at the 4 week time point in both sham and brain injured rats and additionally attenuated the injury induced increase in the excitability of neurons and the frequency of spontaneous EPSCs . The effect of progesterone on cellular excitability changes after injury may be related to its ability to decrease the mRNA expression of the 3 subunit of the voltage gated sodium channel and increase the expression of the neuronal excitatory amino acid transporter 3 in the medial PFC in sham and brain injured animals and also increase glutamic acid decarboxylase mRNA expression in sham but not brain injured animals . Progesterone treatment did not affect injury induced changes in the EPM test . These results demonstrate that administration of progesterone immediately after TBI in 11 day old rats reduces cognitive deficits in adolescence which may be mediated by progesterone mediated regulation of excitatory signaling mechanisms within the medial PFC . | TBI in 11 day old rats results in cognitive deficits in adolescence. TBI results in increased excitatory drive in medial prefrontal cortex neurons. Progesterone attenuates both cognitive deficits and neuronal hyperexcitability. |
S0014488620301618 | Chronic hyperammonemia is a common condition affecting individuals with inherited urea cycle disorders resulting in progressive cognitive impairment and behavioral abnormalities . Altered neurotransmission has been proposed as major source of neuronal dysfunction during chronic hyperammonemia but the molecular pathomechanism has remained incompletely understood . Here we show that chronic exposure to ammonium acetate induces locomotor dysfunction and abnormal feeding behavior in zebrafish larvae indicative for an impairment of higher brain functions . Biochemically chronically elevated ammonium concentrations cause enhanced activity of glutamate decarboxylase isoforms GAD1 and GAD2 with increased formation of GABA and concomitant depletion of glutamate ultimately leading to a dysfunctional hypoglutamatergic and hyperGABAergic metabolic state . Moreover elevated GABA concentrations are accompanied by increased expression of GABA | Chronic hyperammonemia induces locomotor dysfunction and abnormal feeding behavior. Increased GAD activity causes hypoglutamatergic and hyperGABAergic alterations. Expression of GABA. receptor subunits alpha 1 gamma 2 and delta is upregulated. Propionate oxidation sufficiently compensates for the withdrawal of 2 oxoglutarate. |
S0014488620301655 | The present review explores the concept of learning within the context of neurorehabilitation after spinal cord injury . The aim of physical therapy and neurorehabilitation is to bring about a lasting change in functionto encourage learning . Traditionally it was assumed that the adult spinal cord is hardwiredimmutable and incapable of learning . Research has shown that neurons within the lower spinal cord can support learning after communication with the brain has been disrupted by means of a thoracic transection . Noxious stimulation can sensitize nociceptive circuits within the spinal cord engaging signal pathways analogous to those implicated in brain dependent learning and memory . After a spinal contusion injury pain input can fuel hemorrhage increase the area of tissue loss and undermine long term recovery . Neurons within the spinal cord are sensitive to environmental relations . This learning has a metaplastic effect that counters neural over excitation and promotes adaptive learning through an up regulation of brain derived neurotrophic factor . Exposure to rhythmic stimulation treadmill training and cycling also enhances the expression of BDNF and counters the development of nociceptive sensitization . SCI appears to enable plastic potential within the spinal cord by down regulating the Cl | Spinal cord injury SCI enables plasticity by reducing GABA dependent inhibition. Pain input after SCI induces sensitization fosters hemorrhage and impairs recovery. Controllable predictable stimulation increases BDNF and promotes adaptive plasticity. Neurorehabilitative strategies that involve relational learning have a lasting effect. Procedures that introduce periodic regular stimulation promote adaptive plasticity |
S0014488620301667 | Severe traumatic brain injury is the major cause of long term even life long disability and cognitive impairments in young adults . The lack of therapeutic approaches to improve recovery in the chronic phase of severe TBI is a big challenge to the medical research field . Using a single severe TBI model in young adult mice this study examined the restorative efficacy of two hematopoietic growth factors stem cell factor and granulocyte colonystimulating factor on brain repair in the chronic phase of TBI . SCF and G CSF alone or combination treatment was administered at 3months post TBI . Functional recovery was evaluated by neurobehavioral tests during the period of 21weeks after treatment . Neuropathology was examined 22weeks after treatment . We observed that severe TBI caused persistent impairments in spatial learning memory and somatosensory motor function long term and widespread neuropathology including dendritic reduction decrease and overgrowth of axons over generated excitatory synapses and demyelination in the cortex hippocampus and striatum . SCF G CSF and SCF G CSF treatments ameliorated severe TBI induced widespread neuropathology . SCF G CSF treatment showed superior efficacy in improving long term functional outcome enhancing neural plasticity rebalancing neural structure networks disturbed by severe TBI and promoting remyelination . These novel findings demonstrate the therapeutic potential of SCF and G CSF in enhancing recovery in the chronic phase of severe TBI . | SCF G CSF treatment in chronic severe TBI improves long term functional recovery. SCF G CSF treatment rebalances severe TBI induced overgrown of axons and synapses. SCF G CSF treatment in the chronic phase of severe TBI enhances remyelination. |
S0014488620301679 | Neutrophils are considered key participants in post ischemic stroke inflammation . They are the first white blood cells to arrive in ischemic brain and their presence in the brain tissue positively correlates with post ischemic injury severity . CXCL1 is a neutrophil attractant chemokine and the present study evaluates whether redirecting neutrophil migration using a peripherally implanted CXCL1 soaked sponge can reduce brain inflammation and improve outcomes in a novel mouse model of thromboembolic stroke . TE stroke was induced by injection of a platelet rich microemboli suspension into the internal carotid artery of adult C57BL 6 male mice . The model induced neuroinflammation that was associated with increases in multiple brain and serum cytokines chemokines at the mRNA and protein levels including very marked increases in CXCL1 . In other groups of animals an absorbable sterile hemostatic sponge previously immersed in either saline or CXCL1 was implanted into subcutaneous pockets formed in the inguinal region on the left and right side following stroke surgery . Mice implanted with the sponge soaked with CXCL1 had significantly reduced neuroinflammation and infarct size after TE stroke compared to mice implanted with the sponge soaked with 0.9 NaCl . There was also reduced mortality and improved neurological deficits in the TE stroke CXCL1 sponge group compared to the TE stroke 0.9 NaCl sponge group . In conclusion redirecting bloodstream leukocytes toward a peripherally implanted neutrophil chemokine CXCL1 soaked sponge improves outcomes in a novel mouse model of thromboembolic stroke . The present findings suggest a novel therapeutic strategy for patients with acute stroke . | Novel mouse thromboembolic stroke model induced with platelet rich microemboli. Model increased brain CXCL1 levels and induced neutrophil accumulation in brain. A peripherally implanted CXCL1 soaked sponge redirected neutrophils from brain. The implant improved neurological outcome and reduced neuroinflammation in mice. Redirecting neutrophil migration is a novel therapeutic strategy to treat stroke. |
S0014488620301849 | Cerebral edema is a clinical problem that frequently follows ischemic infarcts . Sulfonylurea receptor 1 is an inducible protein that can form a heteromultimeric complex with aquaporin 4 that mediate the ion water transport involved in brain tissue swelling . Transcription of the | Resveratrol reduces brain edema formation and increases survival in the MCAO model of ischemia. Resveratrol reduces DNA binding activity of the transcription factor SP1 in cerebral ischemia. Induced SUR1 expression in the brain during ischemia is down regulated by resveratrol. |
S0014488620301850 | Chemotherapy induced sensorimotor disabilities including gait and balance disorders as well as physical fatigue often persist for months and sometimes years into disease free survival from cancer . While associated with impaired sensory function chronic sensorimotor disorders might also depend on chemotherapy induced defects in other neuron types . In this report we extend consideration to motoneurons which if chronically impaired would necessarily degrade movement behavior . The present study was undertaken to determine whether motoneurons qualify as candidate contributors to chronic sensorimotor disability independently from sensory impairment . We tested this possibility in vivo from rats 5weeks following human scaled treatment with one of the platinum based compounds oxaliplatin widely used in chemotherapy for a variety of cancers . Action potential firing of spinal motoneurons responding to different fixed levels of electrode current injection was measured in order to assess the neurons intrinsic capacity for stimulus encoding . The encoding of stimulus duration and intensity corroborated in untreated control rats was severely degraded in oxaliplatin treated rats in which motoneurons invariably exhibited erratic firing that was unsustained unpredictable from one stimulus trial to the next and unresponsive to changes in current strength . Direct measurements of interspike oscillations in membrane voltage combined with computer modeling pointed to aberrations in subthreshold conductances as a plausible contributor to impaired firing behavior . These findings authenticate impaired spike encoding as a candidate contributor to in the case of motoneurons deficits in mobility and fatigue . Aberrant firing also becomes a deficit worthy of testing in other CNS neurons as a potential contributor to perceptual and cognitive disorders induced by chemotherapy in patients . | Chemotherapy chronically impairs motoneuron repetitive firing. Deficits were restricted to intrinsic spike encoding properties contained in the central nervous system. Neurons exhibit reduced firing probability unpredictable firing frequencies and abolished control of rate modulation. Impaired balance in subthreshold NaPIC and Kv1 conductances exposed as likely biophysical mechanism. Impaired motoneuron firing necessarily produces chronic movement disorders and fatigue experienced by cancer survivors. |
S0014488620301862 | Large peripheral nerve defects require bridging substrates to restore tissue continuity and permit the regrowth of sensory and motor axons . We previously showed that cell free PN segments repopulated | Schwann cells genetically engineered to express different neurotrophic factors. Transduced Schwann cells added to nerve sheaths prior to peroneal nerve engraftment. Graft morphology and the amount of axon regeneration varied between graft types. The type of sensory neuron that regenerated varied depending on neurotrophic factor. There were more regenerating NeuN negative motor neurons in NT 3 nerve grafts. |
S0014488620301874 | Alterations in attention and inhibitory control are common features in several neurological disorders . Environmental factors such as exposure to pesticides have been linked to their appearance . Chlorpyrifos is one of the most widely used organophosphate compounds in the world . CPF exposure during development seems to be critical for later behavioral and molecular disruptions during adult ages although this depends on the specific period of development where the preweaning period is one of the least studied . Despite the abundant empirical work made in the last decades on developmental CPF exposure the systematic study of this on attention is sparse and nonexistent concerning inhibitory control without a single study on preweaning developmental stages . The present research explored the effects of the exposure to low doses of CPF that do not elicit a significant inhibition of the Cholinesterases during this developmental period on rats behavior in the five choice serial reaction time task . Behavioral manipulations pharmacological manipulations and brain gene expression analyses were also conducted . Exposure to CPF decreased the locomotor activity and enhanced the learning profile of the female rats increased the impulsive rates unmasked by a longer inter trial interval hypo sensitized the cholinergic system and down regulated the mRNA expression levels of the brain derived neurotrophic factor in the dorsal striatum of the male rats . This happened without significant inhibition of the brain Acetylcholinesterase . All this new information corroborates that the exposure to a common pesticide at low doses during a key but under explored developmental period importantly affects different behaviors neurotransmitter systems and molecules that are altered in the main neurological disorders observed nowadays . | CPF exposure decreased adult females locomotor activity. CPF exposure enhanced adult females learning rates at the early stages. Longer ITI unmasked an impulsive profile in the CPF exposed animals. CPF exposed animals were hyposensitive to a cholinergic system challenge. CPF exposure drastically reduced BDNF mRNA levels in the dorsal striatum. |
S0014488620301886 | Cognitive dysfunction is one of the most disabling non motor symptoms of Parkinson s disease though its pathological correlates still remain elusive . Hippocampal Lewy pathology has recently been correlated by compelling evidence from post mortem and imaging studies . Animal models recapitulating cognitive impairment in PD are essential to better understand the underlying pathophysiology . To investigate the hippocampal involvement in cognitive dysfunction of PD we generated an experimental model by inducing midbrain and hippocampal synuclein pathology simultaneously . Rats were injected either with human synuclein or green fluorescent protein expressing adeno associated viral vectors or saline bilaterally into substantia nigra and dentate gyrus . A group of untreated animals were used as nave controls . Cognitive and behavioral changes were evaluated with tests probing for spatial learning short term memory anxiety and hedonistic behavior . Immunohistochemical staining immunoblotting and stereological analysis were performed for pathological characterization . Bilateral synuclein overexpression in SN and DG led to mild but significant motor impairment as well as dysfunctions in short term memory and spatial learning . There was no hedonistic deficit whereas a hypo anxious state was induced . While stereological analysis revealed no significant neuronal loss in any sectors of cornu ammonis there was considerable decrease in TH Bilateral synuclein overexpression in DG and SN reproduced partial motor and hippocampus related cognitive deficits . Using this model we showed a predisposition of CA2 for pathological synuclein accumulation which may provide further insights for future experimental and clinical studies . | rAAV5 h synuclein injected bilaterally both into substantia nigra and dentate gyrus. Synuclein overexpressing animals showed mild but significant motor and cognitive impairments. Synuclein overexpression lead to TH. neuronal loss in SN with decreased synaptophysin levels in striatum. Despite no significant neuronal loss in hippocampus decreased synaptophysin levels suggested synaptic degeneration. Among hippocampal subregions CA2 was the most affected area with dense p Ser129 synuclein accumulation. |
S0014488620301898 | Huntington s disease is a dominantly inherited neurodegenerative disease caused by a polyglutamine expansion in the widely expressed huntingtin protein . Multiple studies have indicated the importance of mutant huntingtin in astrocytes to HD pathogenesis . Astrocytes exhibit SNARE dependent exocytosis and gliotransmission which can be hampered by transgenic expression of dominant negative SNARE in these glial cells . We used BACHD mice and crossed them with the dnSNARE model to determine if pan astrocytic SNARE dependent exocytosis plays an important role in vivo in the progression of HD behavioral phenotypes . We assessed motor and neuropsychiatric behaviors in these mice . At 12months of age there was a significant improvement in motor coordination in BACHD dnSNARE mice when compared to BACHD mice . Analyses of open field performance revealed significant worsening of center entry but not distance traveled in BACHD dnSNARE when compared to BACHD mice and variable inconclusive results on vertical plane entry . While no differences between BACHD and BACHD dnSNARE mice at 12months of age in the forced swim test were found we did observe a significant decrease in performance of BACHD dnSNARE mice in the light dark box paradigm . Thus reduction of astrocytic SNARE dependent exocytosis has differential effects on the psychiatric like and motor phenotypes observed in BACHD mice . These data suggest broadly targeting SNARE dependent exocytosis in astrocytes throughout the brain as a means to modulate gliotransmission in HD may contribute to worsening of specific behavioral deficits and perhaps a brain region specific approach would be required . | Using transgenic dnSNARE expression to block astrocytic SNARE dependent exocytosis has differential effects on behavior. Hampering astrocytic SNARE dependent exocytosis improved motor coordination in BACHD mice. BACHD mice were more anxious after a reduction in astrocytic SNARE dependent exocytosis. |
S0014488620301904 | The activation of tyrosine kinase receptor c Met by hepatocyte growth factor showed an anti apoptotic effect in numerous disease models . This study aimed to investigate the neuroprotective mechanism of the HGF c Met axis mediated anti apoptosis underlying the delayed recanalization in a rat model of middle cerebral artery occlusion . Permanent MCAO model was induced by intravascular filament insertion . Recanalization was induced by withdrawing the filament at 3days after MCAO . HGF levels in the blood serum and brain tissue expressions of HGF c Met phosphorylated STAT3 STAT3 Bcl 2 Bax cleaved caspase 3 were assessed using ELISA and western blot respectively . To study the mechanism HGF small interfering ribonucleic acid and c Met inhibitor su11274 were administered intracerebroventricularly or intranasally respectively . The concentration of HGF in the serum was increased significantly after MCAO . Brain expression of HGF was increased after MCAO and peaked at 3days after recanalization . HGF and c Met were both co localized with neurons . Compared to rats received permanent MCAO delayed recanalization after MCAO decreased the infarction volume inhibited neuronal apoptosis and improved neurobehavioral function increased expressions of p STAT3 and its downstream Bcl 2 . Mechanistic studies indicated that HGF siRNA and su11274 reversed the neuroprotection including anti apoptotic effects provided by delayed recanalization . In conclusion the delayed recanalization after MCAO increased the expression of HGF in the brain and reduced the infarction and neuronal apoptosis after MCAO partly via the activation of the HGF c Met STAT3 Bcl 2 signaling pathway . The delayed recanalization may serve as a therapeutic alternative for a subset of ischemic stroke patients . | Delayed recanalization at 3days after MCAO decreases infarction and improves neurobehavioral score in rats. Apoptosis can be detected at 6days after permanent MCAO and it is inhibited by delayed recanalization. HGF c Met pathway plays an important role in anti apoptotic effect observed after delayed recanalization. |
S0014488620301928 | The morphology and projections of ventral horn interneurones in the segment above an ipsilateral thoracic lateral spinal cord lesion were studied in the cat by intracellular injections of Neurobiotin at 6 to 18weeks post lesion and compared with previously published control data from uninjured spinal cords . The cell axons ascended descended or both mostly contralaterally and mostly spared by the lesion . Unusual morphological dendritic features were seen in the lesion group mostly growth related including complex dendritic appendages twisted or multiple branched terminal dendrites commissural dendrites apparently swollen proximal dendrites and rostrocaudal asymmetries . Significant quantitative differences included more dendritic spines in the lesion group and smaller soma areas in the lesion group . Immunoreactivity to microtubule associated protein 2a b was detected in the proximal but not distal dendrites of cells in the lesion group corresponding to an overall decrease in immunoreactivity in the ventral horns on the lesion side compared to the other . For axon collaterals significant increases for the lesion group were seen in the number of collaterals in the first 4mm of axon and in the area of ventral intermediate horn occupied by terminals including increased innervation of some regions among which were the intermediolateral columns . This dendritic and axonal plasticity makes the interneuones candidates for a role in detour circuits but also for a maladaptive role in autonomic hyperreflexia . | Thoracic interneurones above a spinal cord injury were intracellularly labelled. This uncovered significant dendritic plasticity on interneurones. Interneurones had more axon collateral branches and larger termination areas. The axon collateral branches also terminated in new areas. These changes may have involved detour circuits but also may have been maladaptive. |
S001448862030193X | The present study was designed to investigate the potential role and the mechanism of equilibrative nucleoside transporter 1 on neuronal apoptosis and neurological deficits after middle cerebral artery occlusion in rats . One hundred and thirty four male Sprague Dawley rats were subjected to two hours of MCAO followed by reperfusion . The time course of the expression level of ENT1 and phosphorylation of CREB were detected by western blot and immunofluorescence staining . Another set of animals were administrated with NBTI the ENT1 inhibitor by daily intraperitoneal injection starting at 0.5h post MCAO infarction volume and neurological deficits were measured both at 24h and 72h post MCAO . We further explored the neuroprotection machenism by using H89 cAMP dependent protein kinase inhibitor the expression of Bcl 2 Bax phosphorylated CREB and Cleaved caspase 3 were quantified by Western blot neuronal apoptosis were analyed by TUNEL staining . The endogenous expression of ENT1 were significantly increased and peaked at 12h after MCAO . High dose of NBTI reduced brain infarction volume and improved neurologic deficits both at 24h and 72h post MCAO . Moreover NBTI significantly increased the level of CREB phosphorylation and extracellular adenosine concentration and decreased the neuronal apoptosis 24h after MCAO . NBTI treatment reduced the expression of Bax and cleaved caspase 3 while up regulated Bcl 2 compared with vehicle group . These effects were abolished by H89 pretreatment . ENT1 inhibition prevented neuronal apoptosis and improves neurological deficits through cAMP PKA CREB Bcl 2 signaling pathway after MCAO in rats . ENT1 might be an effective target in the treatment strategy for ischemic stroke . | The expression time course of equilibrative nucleoside transporter ENT1 after MCAO in rats. ENT1 inhibitior NBTI 15 mg kg reduced infarct volume and improved neurological function 24 and 72 hours after MCAO. NBTI treatment reversed the depletion of extracellular adenosine concentration and CREB phosphorylation after MCAO. NBTI treatment prevented neural apoptosis though the cAMP pCREB Bcl2 signal pathway |
S0014488620301941 | Acellular nerve allografts are increasingly used to repair nerve gaps following injuries . However these nerve scaffolds have yet to surpass the regenerative capabilities of cellular nerve autografts improved understanding of their regenerative mechanisms could improve design . Due to their acellular nature both angiogenesis and diverse cell recruitment is necessary to repopulate these scaffolds to promote functional regeneration . We determined the contribution of angiogenesis to initial cellular repopulation of ANAs used to repair nerve gaps as well as the signaling that drives a significant portion of this angiogenesis . Wild type mice with nerve gaps repaired using ANAs that were treated with an inhibitor of VEGF receptor signaling severely impaired angiogenesis within ANAs as well as hampered cell repopulation and axon extension into ANAs . Similarly systemic depletion of hematogenous derived macrophages but not neutrophils in these mice models severely impeded angiogenesis and subsequent nerve regeneration across ANAs suggesting hematogenous derived macrophages were major contributors to angiogenesis within ANAs . This finding was reinforced using CCR2 knockout models . As macrophages represented the majority of CCR2 expressing cells a CCR2 deficiency impaired angiogenesis and subsequent nerve regeneration across ANAs . Furthermore an essential role for CCL2 during nerve regeneration across ANAs was identified as nerves repaired using ANAs had reduced angiogenesis and subsequent nerve regeneration in CCL2 KO vs WT mice . Our data demonstrate the CCL2 CCR2 axis is important for macrophage recruitment which promotes angiogenesis cell repopulation and subsequent nerve regeneration and recovery across ANAs used to repair nerve gaps . | Nerve gaps repaired using ANAs require VEGF signaling for cell repopulation. Hematogenous derived CCR2 macrophages promote angiogenesis within ANAs. CCL2 signaling recruits macrophages within ANAs. A deficiency in CCL2 CCR2 signaling impairs nerve regeneration and recovery. |
S0014488620301953 | Owing to its potent longterm neuroprotective and neurorestorative properties glial cell line derived neurotrophic factor is currently studied in neurodegenerative disease clinical trials . However little is known about the longterm effect of GDNF on neurological recovery brain remodeling and neuroplasticity in the post acute phase of ischemic stroke . In a comprehensive set of experiments we examined the effects of lentiviral GDNF administration after ischemic stroke . GDNF reduced neurological deficits neuronal injury blood brain barrier permeability in the acute phase in mice . As compared with control enhanced motor coordination and spontaneous locomotor activity were noted in GDNF treated mice which were associated with increased microvascular remodeling increased neurogenesis and reduced glial scar formation in the peri infarct tissue . We observed reduced brain atrophy and increased plasticity of contralesional pyramidal tract axons that crossed the midline in order to innervate denervated neurons in the ipsilesional red and facial nuclei . Contralesional axonal plasticity by GDNF was associated with decreased abundance of the axonal growth inhibitors brevican and versican in contralesional and ipsilesional brain tissue reduced abundance of the growth repulsive guidance molecule ephrin b1 in contralesional brain tissue increased abundance of the midline growth repulsive protein Slit1 in contralesional brain tissue and reduced abundance of Slit1 s receptor Robo2 in ipsilesional brain tissue . These data indicate that GDNF potently induces longterm neurological recovery peri infarct brain remodeling and contralesional neuroplasticity which are associated with the fine tuned regulation of axonal growth inhibitors and guidance molecules that facilitate the growth of contralesional corticofugal axons in the direction to the ipsilesional hemisphere . | GDNF improves Blood Brain Barrier permeability in acute phase of brain injury. improves functional recovery which is associated with microvascular and tissue remodeling in subacute phase of brain injury. increases contralesional pyramidal tract plasticity. regulates axonal outgrowth and repulsive guidance molecules. |
S0014488620302041 | Neurofibromatosis type 1 is associated with higher rates of epilepsy compared to the general population . Some NF1 patients with epilepsy do not have intracranial lesions suggesting the genetic mutation itself may contribute to higher rates of epilepsy in these patients . We have recently demonstrated increased seizure susceptibility in the Young male or female adult The average initial neocortical after discharge threshold was significantly lower in the We have demonstrated for the first time an increased rate of epileptogenesis in an animal model of NF1 with no known macroscopic neoplastic brain lesions . This work provides evidence for the genetic mutation itself playing a role in seizures and epilepsy in patients with NF1 and supports the use of the | mice have a faster neocortical kindling progression than WT mice. A subset of. mice develop SRSs after hippocampal or neocortical kindling which is not seen in WT mice. Electrical kindling induces an increase in the ratio of phosphorylated Akt and Erk proteins. Increased epileptogenicity in a non lesional model of. suggests the genetic mutation itself contributes to increased seizures and epilepsy. |
S0014488620302053 | Receptor interacting protein kinase 3 regulates a newly discovered cell death form called necroptosis . RIPK3 nuclear translocation and inflammatory factor release are involved in necroptosis after rat global cerebral ischemia reperfusion injury . The purpose of this study was to investigate the effects of interactions between the RIPK3 and apoptosis inducing factor necroptosis pathway and the JNK mediated inflammatory pathway . Rats were subjected to 4 vessel occlusion and reperfusion injury . RIPK3 inhibitor GSK872 RIPk3 recombinant adeno associated virus and JNK specific inhibitor SP600125 were intracerebroventricular injected before I R. Hippocampus CA1 tissue were obtained and RIPK3 AIF p JNK IL 6 were determined by western blot analysis . The RIPK3 and AIF interaction were also analyzed by immunofluorescence and immunoprecipitation . The expression of endogenous RIPK3 AIF p JNK and IL 6 was increased in hippocampus CA1 in I R group . In addition RIPK3 was increased in both the total protein and nuclear protein . GSK872 administration reduced the number of neuron deaths and the expression of RIPK3 p JNK and IL 6 . GSK872 also improve the rat neurobehavior . While use RIPk3 rAAV treatment to overexpress RIPK3 it appeared lower neuron survival . Immunofluorescence staining demonstrated that RIPK3 and AIF formed as a novel complex in the cytoplasm first and then nuclear translocation . GSK872 pretreatment decreased the number of RIPK3 positive cells and related to the generation of RIPK3 AIF complex in nuclear . Moreover the production of inflammatory factors levels was found to be significantly elevated after I R. We further use SP600125 to attenuate inflammation cascade . It not only inhibits the expression of inflammatory factors p JNK and IL 6 but also inhibits RIPK3 and AIF in the cytoplasm . Collectively the results of our study indicate that RIPK3 mediated necroptosis interacts with the JNK mediated inflammatory signaling pathway to participate in global cerebral I R injury . JNK regulated inflammatory mediators may promote the necroptosis initiation . | RIPK3 AIF complex nuclear transfer mediates cell death after I R injury. Inhibitor GSK872 attenuates RIPK3 AIF complex enrichment in nucleus. Regulation of RIPK3 affects the JNK and IL 6 induced inflammation. JNK inflammatory signaling promotes the necroptosis initial. |
S0014488620302077 | Mechano growth factor is an alternatively spliced form of insulin like growth factor 1 that has shown to be neuroprotective against 6 hydroxydopamine toxicity and ischemic injury in the brain . MGF also induces neural stem cell proliferation in the hippocampus and preserves olfactory function in aging mice . Cisplatin is a chemotherapy drug that induces peripheral neuropathy in 3040 of treated patients . Our studies were designed to see if MGF would protect dorsal root ganglion neurons from cisplatin induced neurotoxicity and to identify potential mechanisms that may be involved . Expression of endogenous MGF in adult DRG neurons | MGF prevents cisplatin induced thermal hyperalgesia. MGF and CMGF is protective against cisplatin induced cell death. MGF binds nucleolin and nucleolin antibody prevents protection. |
S0014488620302089 | Neurogenic bowel following spinal cord injury leads to decreased colonic motility remodeling of the neuromuscular compartment and results in chronic evacuation difficulties . The distal colon of the rat serves a dual role for fluid absorption and storage that is homologous to the descending colon of humans . Dysmotility of the descending colon is one component of neurogenic bowel . We investigated the integrity of the enteric neuromuscular transmission responsible for the generation of excitatory and inhibitory junction potentials in the distal colon of rats . We previously demonstrated a chronic reduction in colonic enteric neurons from rats with acute and chronic high thoracic SCI and hypothesized that neurogenic bowel following T3 SCI results from diminished enteric neuromuscular transmission . | Inhibitory myenteric nNOS immunoreactive cells are reduced by injury. Excitatory neuromuscular signaling is diminished following spinal cord injury. Nitrergic slow inhibitory neuromuscular signaling is diminished following SCI. Purinergic fast inhibitory neuromuscular signaling was unaffected by SCI. Excitatory myenteric choline acetyltransferase immunopositive cells are reduced by injury |
S0014488620302090 | Soldiers are often exposed to more than one traumatic brain injury over the course of their service . In recent years more attention has been drawn to the increased risk of neurological deficits caused by the blast plus polytrauma which typically is a blast trauma combined with other forms of TBI . In this study we investigated the behavioral and neuronal deficits resulting from a blast plus injury involving a mild moderate blast followed by a mild blunt trauma using the fluid percussion injury model . We identified that the blast injury predisposed the brain to increased cognitive deficits chronic ventricular enlargement increased neurodegeneration at acute time points and chronic neuronal loss . Interestingly a single blast and single blunt injury differed in their onset and manifestation of cognitive and regional neuronal loss . We also identified the presence of cleaved RIP1 from caspase 8 mediated apoptosis in the blunt injury while the blast injury did not activate immediate apoptosis but led to decreased hilar neuronal survival over time . | Blast exposure predisposed the brain to increased neurological deficits on a subsequent blunt traumatic brain injury TBI . Blast and blunt TBI differed in the development of neurodegeneration and behavioral deficits. Blast TBI resulted in chronic hilar neuronal loss numbers similar to blunt TBI. |
S0014488620302119 | The trichothiodystrophy group A protein functions in nucleotide excision repair and basal transcription . TTDA plays a role in cancers and serves as a prognostic and predictive factor in high grade serous ovarian cancer however its role in human glioma remains unknown . Here we found that TTDA was overexpressed in glioma tissues . In vitro experiments revealed that TTDA overexpression inhibited apoptosis of glioma cells and promoted cell growth whereas knockdown of TTDA had the opposite effect . Increased TTDA expression significantly decreased the Bax Bcl2 ratio and the level of cleaved caspase3 . TTDA interacted with the p53 gene at the 1959bp and 1530bp region and regulated its transcription leading to inhibition of the p53 Bax Bcl2 mitochondrial apoptosis pathway in glioma cells . These results indicate that TTDA is an upstream regulator of p53 mediated apoptosis and acts as an oncogene suggesting its value as a potential molecular target for the diagnosis and treatment of glioma . | TTDA was up regulated in glioma tissues and acted as an oncogene. TTDA promoted cell proliferation and inhibited mitochondrial apoptosis in glioma cells. TTDA inhibited glioma cell apoptosis through the p53 Bax Bcl2 mitochondrial pathway. TTDA was an upstream regulator of p53 mediated apoptosis and bound with the p53 gene to inhibit the transcription of p53. |
S0014488620302120 | Spinal cord injury is a severe condition resulting in specific neurological symptoms depending on the level of damage . Approximately 60 of spinal cord injuries affect the cervical spinal cord resulting in complete or incomplete tetraplegia and higher mortality rates than injuries of the thoracic or lumbar region . Although cervical spinal cord injuries frequently occur in humans there are few clinically relevant models of cervical spinal cord injury . Animal models are critical for examining the cellular and molecular manifestations of human cervical spinal cord injury which is not feasible in the clinical setting and to develop therapeutic strategies . There is a limited number of studies using cervical bilateral contusion SCI and providing a behavioral assessment of motor and sensory functions which is partly due to the high mortality rate and severe impairment observed in severe cervical SCI models . The goal of this study was to develop a mouse model of cervical contusion injury with moderate severity resulting in an apparent deficit in front and hindlimb function but still allowing for self care of the animals . In particular we aimed to characterize a mouse cervical injury model to be able to use genetic models and a wide range of viral techniques to carry out highly mechanistic studies into the cellular and molecular mechanisms of cervical spinal cord injury . After inducing a bilateral cervical contusion injury at level C5 we followed the recovery of injured and sham uninjured animals for eight weeks post surgery . Hindlimb and forelimb motor functions were significantly impaired immediately after injury and all mice demonstrated partial improvement over time that remained well below that of uninjured control mice . Mice also displayed a significant loss in their sensory function throughout the testing period . This loss of sensory and motor function manifested as a reduced ability to perform skilled motor tasks in all of the injured mice . Here we describe a new mouse model of moderate bilateral cervical spinal cord injury that does not lead to mortality and provides a comprehensive assessment of histological and behavioral assessments . This model will be useful in enhancing our mechanistic understanding of cervical spinal cord injury and in the development of treatments targeted at promoting neuroprotection neuroplasticity and functional recovery after cervical SCI . | Description of a model for cervical spinal cord injury. Moderate bilateral contusion injury. Comprehensive behavioral assessment. |
S0014488620302144 | In the brain murine double minute 2 an E3 ubiquitin ligase modulates neuronal excitability by regulating glutamate receptor and postsynaptic density 95 levels through ubiquitination . Thus Mdm2 is relevant to epileptic seizures in human patients . Although phosphorylation at serine 166 site by AKT increases Mdm2 activity phosphatases of Mdm2 have been still elusive . Here we demonstrate the novel function of pyridoxal 5 phosphate phosphatase chronophin in Mdm2 dephosphorylation that may negatively regulate PSD95 ubiquitination . As compared to wild type mice PLPP CIN knockout | KA induced seizure activity increases PLPP CIN mediated Mdm2 S166 dephosphorylation. PLPP CIN mediated Mdm2 S166 dephosphorylation increases Mdm2 ubiquitination. PLPP CIN mediated increase in Mdm2 ubiquitination inhibits PSD95 ubiquitination. PLPP CIN mediated Mdm2 ubiquitination increases PSD95 NR2A binding. PLPP CIN inhibition may be a potential therapeutic target for epilepsy. |
S001448862030217X | Intracerebral hemorrhage is the common brain diseases in middle aged and elderly people with high disability and or mortality rate and is a serious public health concern . Both WNK3 kinase and the WNK3 SPAK NKCC1 signaling pathway play an integral role in maintaining normal cell homeostasis . However their role and underlying mechanisms in ICH induced secondary brain injury have yet to be elucidated . We established an ICH model using male Sprague Dawley rats by injecting autologous arterial blood into the unilateral basal ganglia . To establish ICH model Our data showed that WNK3 expression in brain tissue were upregulated after ICH induction . In addition silencing of WNK3 reduced neuronal apoptosis and inflammatory responses in rats that underwent ICH . Inhibition of WNK3 expression reduced the damaged blood brain barrier alleviated the impaired degree of cerebral edema and improved disruptive neurobehavioral cognition caused by ICH . Moreover overexpression of WNK3 had the opposite effects . Finally WNK3 SPAK NKCC1 signaling pathway may be involved in the above mentioned processes . In conclusion our findings showed that WNK3 and WNK3 SPAK NKCC1 signaling pathway play a vital biological function in ICH induced SBI . Depletion of WNK3 attenuated brain injury after ICH both | Protein levels of WNK3 increased significantly in brain tissues after ICH. Decreasing of WNK3 played neuroprotective effects in rats after ICH. Inhibition of WNK3 decreased OxyHb induced neuronal apoptosis. WNK3 participated in ICH induced secondary brain injury. |
S0014488620302181 | The transcription factor nuclear factor erythroid 2 related factor 2 is known to induce neuroprotective and anti inflammatory effects and is considered to be an excellent molecular target for drugs related to neurodegenerative disease therapy . Nrf2 activators previously tested in clinical trials were electrophilic causing adverse effects due to non selective and covalent modification of cellular thiols . In order to circumvent this issue we constructed and screened a chemical library consisting of 241 pyrazolo 3 4 | KKC080106 was selected from a pyrazolo 3 4. pyrimidine library we constructed. It binds to Keap1 activates Nrf2 and elevates Nrf2 target gene expression. It suppresses the inflammatory signaling and production of the inflammatory markers. It prevents MPTP induced neurodegeneration microglial activation and motor deficits. It exhibits good safety and pharmacokinetic profiles as a CNS drug. |
S0014488620302193 | CDKL5 deficiency disorder is a devastating neurodevelopmental disorder characterized by early onset epilepsy severe intellectual disability cortical visual impairment and motor disabilities . Epilepsy is a central feature of CDD with most patients having intractable seizures but seizure frequency and severity can vary . Clinical reports demonstrate a diversity in seizure semiology and electrographic features with no pattern diagnostic of CDD . Although animal models of CDD have shown evidence of hyperexcitability spontaneous seizures have not been previously reported . Here we present the first systematic study of spontaneous seizures in mouse models of CDD . Epileptic spasms the most frequent and persistent seizure type in CDD patients were recapitulated in two mouse models of CDD carrying heterozygous mutations | First report of spontaneous seizures in mouse models of CDKL5 deficiency disorder CDD . Characterization of the ictal and interictal features of epileptic spasms in. mutant mice. Analysis of the diurnal variation in EEG background abnormalities. |
S001448862030220X | Chronic cerebral hypoperfusion promotes the development of Alzheimer s pathology . However whether and how CCH impairs the synaptic vesicle trafficking is still unclear . In the present study we found that the hippocampal glutamatergic vesicle trafficking was impaired as indicated by a significant shortened delayed response enhancement phase in CA3 CA1 circuit and decreased synapsin I in CCH rats suffering from bilateral common carotid artery occlusion . Further study showed an upregulated | Chronic cerebral hypoperfusion impairs hippocampal glutamatergic vesicle trafficking. MicroRNA 153 binds. and downregulates synapsin I expression. Knockdown of microRNA 153 rescues hippocampal vesicle trafficking in 2VO rats. |
S0014488620302211 | Because environmental elements modify chronic pain development and endogenous mechanisms of pain control are still a great therapeutic source we investigated the effects of an early exposure to environmental enrichment in a translational model of neuropathic pain . Young male rats born and bred in an enriched environment which did not count on running wheel underwent chronic constriction injury of sciatic nerve . EE abolished neuropathic pain behavior 14days after CCI . Opioid receptors antagonism reversed EE analgesic effect . endorphin and met enkephalin serum levels were increased only in EE CCI group . Blockade of glucocorticoid receptors did not alter EE analgesic effect although corticosterone circulating levels were increased in EE animals . In the spinal cord EE controlled CCI induced serotonin increase . In DRG EE blunted the expression of ATF 3 after CCI . Surprisingly EE CCI group showed a remarkable preservation of sciatic nerve fibers compared to NE CCI group . This work demonstrated global effects induced by an EE protocol that explain in part the protective role of EE upon chronic noxious stimulation reinforcing the importance of endogenous mechanisms in the prevention of chronic pain development . | Early environmental enrichment EE attenuates nerve injury outcomes. EE induces endorphin and met enkephalin systemic release after CCI. EE controls spinal CCI induced serotonin increase. Neuropathic markers are differentially expressed in enriched animals after CCI. EE reduces CCI induced Wallerian degeneration. |
S0014488620302223 | Volume regulated anion channels are critically involved in regulating cell volume and leucine rich repeat containing protein 8A is an obligatory subunit of VRACs . Cell swelling occurs early after brain ischemia but it is unclear whether neuronal LRRC8a contributes to ischemia induced glutamate release and brain injury . We found that | Cerebral ischemia transiently increases LRRC8A protein levels in the hippocampus. LRRC8A is essential for hippocampal neuronal VRAC activity increased by ischemia. LRRC8A is required for hypotonicity potentiated glutamatergic input to neurons. LRRC8A dependent VRACs contribute to brain injury caused by cerebral ischemia. |
S0014488620302235 | Although it has been documented that central nervous system pericytes are able to contract in response to physiological pharmacological or pathological stimuli the underlying mechanism of pericyte contractility is incompletely understood especially in downstream pericytes that express low amounts of alpha smooth muscle actin . To study whether pericyte contraction involves F actin polymerization as in vascular smooth muscle cells we increased retinal microvascular pericyte tonus by intravitreal injection of a vasoconstrictive agent noradrenaline . The contralateral eye of each mouse was used for vehicle injection . The retinas were rapidly extracted and fixed within 2min after injections . Polymeric filamentous and monomeric globular forms of actin were labeled by fluorescently conjugated phalloidin and deoxyribonuclease I respectively . We studied 108 and 83 pericytes from 6 NA and 6 vehicle treated retinas and found that F G actin ratio a microscopy based index of F actin polymerization significantly increased in NA treated retinas 4.2 vs. 3.5 | Mechanisms of CNS pericyte contractility are incompletely understood. Noradrenaline promoted F actin polymerization in retinal microvascular pericytes. F actin polymerization was more pronounced in pericytes on downstream capillaries. They contracted tide like suggesting a role for regulating capillary tone and flow. F actin polymerization is needed for contractility of downstream pericytes poor in SMA |
S0014488620302247 | Neonatal hypoxic ischemic brain injury remains a devastating clinical disease associated with high mortality and lifetime disability . Neonatal HI injury damages the architecture of neurovascular unit thus therapy targeting the NVU may provide effective neuroprotection against HI . This study was designed to investigate whether fibroblast growth factor 10 protected the NVU against HI and afforded observable neuroprotection in a rat model of neonatal HI brain injury . The results showed that FGF10 treatment significantly reduced brain damage post HI characterized by reduction in brain infarct volume and tissue loss . Further interesting findings showed that FGF10 treatment exerted neuroprotective effects on HI brain injury in neonate rats through protecting the NVU against HI evidenced by inhibition of neuronal cell apoptosis suppression of gliosis and amelioration of blood brain barrier disruption . Collectively our study indicates that FGF10 treatment exhibits great potential for protecting NVU against HI and attenuates neonatal brain injury suggesting a potential novel therapeutic agent to this disease . | FGF10 decreases neuronal death via inhibiting neuronal apoptosis. FGF10 attenuates the activation of microglia and astrocytes through modulating TLR4 NF B signaling pathway. FGF10 ameliorates blood brain barrier disruption via reducing tight junction and adherens junction proteins degradation and pericytes loss. FGF10 exerts protective effects on the neurovascular unit in a rat model of neonatal HI brain injury. |
S0014488620302259 | MicroRNAs are an abundant class of small non coding regulatory RNAs that operate as prominent modulators of mammalian gene expression . It is now well established that post transcriptional regulation of gene expression plays a vital role in both physiological and pathological processes such as neural development and neural regeneration . The flexibility and efficiency of miRNA function provide precise temporal and spatial gene regulatory capacities that are essential for proper maintenance of neural circuits . The anatomical and functional complexity of the neural system requires absolute coordination of multilayered gene regulatory networks . In this review we characterize microRNA functions involved in the process of neurogenesis from stem cell pluripotent self renewal capability to neural progenitor cell differentiation and from synaptic plasticity and rearrangement to neural cell release of exosomes delivering functional nucleic acids . In particular we summarize the characteristics of biomaterial based tissue engineering approaches such as scaffold fabrication and drug delivery systems and demonstrate the applications of current miRNA based technologies in neural dysfunction of the central and peripheral nervous system . | MicroRNA functions involved in neurogenesis during neural development. MicroRNAs play an essential role in diverse molecular events in stem cells. MicroRNAs hold therapeutic potentials in tissue engineering for neural regeneration. |
S0014488620302260 | Spinal cord injury above the lumbosacral level results in lower urinary tract dysfunction including detrusor hyperreflexia wherein bladder compliance is low and a lack of external urethral sphincter control leading to detrusor sphincter dyssynergia with poor voiding efficiency . Experimental studies in animals have shown a dense innervation of serotonergic fibers and multiple 5 HT receptors in the spinal reflex circuits that control voiding function . Here we investigated the efficacy of NLX 112 in regulating lower urinary tract function after T8 contusive SCI in rats . NLX 112 is a very potent highly selective and fully efficacious 5 HT | NLX 112 improves LUT function after chronic complete SCI. NLX 112 improves LUT function after chronic contusive SCI. The regulation of LUT function by NLX 112 is in a dose dependent manner. The effect of NLX 112 in LUT function can be reversed by its antagonist. |
S0014488620302272 | Huntington disease is an autosomal dominant neurodegenerative disorder caused by an expansion of a polyglutamine repeat in the huntingtin protein . Aberrant activation of caspase 6 and cleavage of mutant HTT generating the toxic N terminal 586 HTT fragment are important steps in the pathogenesis of HD . Similarly alterations in the insulin like growth factor 1 signaling pathway have been implicated in the disease as a result of decreased plasma IGF 1 levels in HD patients . In addition two recent studies have demonstrated therapeutic benefit of IGF 1 treatment in mouse models of HD . Since IGF 1 promotes pro survival pathways we examined the relationship between IGF 1 signaling and aberrant caspase 6 activation in HD . Using immortalized mouse striatal cells expressing wild type or mutant HTT we show that reduced levels of IGF 1 are associated with enhanced activation of caspase 6 increased cell death and mutant HTT cleavage in a cellular stress paradigm . We demonstrate that IGF 1 supplementation reverses these effects and lowers the level of the toxic 586 HTT fragment . In addition transcriptional analysis in the R6 2 HD transgenic mouse model demonstrated that the IGF 1 signaling system is dysregulated at multiple levels in several tissues including liver muscle and brain . Among these changes we found increased expression of IGF 1 binding protein 3 which may further reduce the bioavailability of IGF 1 as a consequence of increased IGF 1 binding . Our findings thus suggest that the therapeutic benefit of IGF 1 supplementation in HD may be significantly improved if other defects in the IGF 1 signaling pathway are corrected concurrently . | Caspase 6 activation mutant 586 HTT fragments and cell death can be reduced by IGF 1. The IGF system is impaired at multiple levels in HD striatal cell and HD mouse tissues. Increasing IGF 1 bioavailability by correcting the IGF 1 signaling system may potentiate its therapeutic benefit. |
S0014488620302296 | We investigated the ability of agmatine to potentiate the antidepressant like and synaptic effects of ketamine in mice . Agmatine and ketamine produced an antidepressant like effect in the tail suspension test . The combination of agmatine and ketamine at subthreshold doses produced an antidepressant like effect 1h 24h and 7d after treatment . Western blot analysis from prefrontal cortex tissue showed that the combined treatment after 1h increased p70S6K and GluA1 and reduced synapsin 1 phosphorylation . Additionally after 24h Akt p70S6K GluA1 and synapsin 1 phosphorylation and PSD95 immunocontent increased . Dendritic architecture analysis of the prefrontal cortex revealed that the combined treatment improved dendritic arbor complexity and increased spine density . Morphometric analysis revealed a filopodia shaped dendrite spine upregulation after 1h . A predominance of stubby mushroom branched and filopodia and a reduction in thin protrusions were observed after 24h . Finally mushroom shaped dendritic spines predominance increased after 7d . Agmatine potentiated ketamine s antidepressant and dendritic arbors and spines remodeling effects in a time dependent manner . Our data indicate Akt p70S6K signaling as a likely target for these effects . | The synergism of agmatine and ketamine produces an antidepressant like effect. Agmatine potentiates ketamine s dendritic arbors and spines remodeling effects. Agmatine s enhancer effects of ketamine involves Akt S6K signaling activation. Agmatine augments ketamine s effects in a time dependent manner. |
S0014488620302302 | After cerebral ischemia reperfusion injury pro inflammatory M1 like and anti inflammatory M2 like phenotypes of microglia are involved in neuroinflammation in which NLRP3 inflammasome plays an essential role . Kv1.3 channel has been recognized as neuro immunomodulatory target but it is not clear as to its role in the neuroinflammation after cerebral ischemic injury . The current study aimed to investigate the issue . Middle cerebral artery occlusion reperfusion model in rats and oxygen glucose deprivation reoxygenation in primary microglia were utilized to mimic disease state of ischemic stroke . Treatment with PAP 1 a Kv1.3 channel blocker produced a significant improvement in neurological deficit scores and a decrease in infarct volume in MCAO R model . An increased number of M2 like phenotypic microglia and a reduced number of M1 like phenotypic microglia were observed by immunofluorescent staining in the in vivo model which was further validated by flow cytometry in vitro . Western blot showed that PAP 1 treatment profoundly reduced cleavage of caspase 1 and IL 1 | Kv1.3 channel blockade produced neuroprotective effect in MCAO R model. Kv1.3 channel blockade reshaped microglial phenotypes from M1 towards M2 and compromised inflammasome activation in microglia after cerebral ischemic injury. Kv1.3 channel blockade may provide a promising neuro immunomodulatory strategy for ischemic stroke. |
S0014488620302326 | Despite the shift in the demographics of traumatic spinal cord injury with increased proportion of injuries in the elderly little is known on the potential effects of old age on the pathobiology of SCI . Since there is an assumption that age adversely affects neural response to SCI this study examines the clinically relevant question on whether age is a key determinant of inflammatory response oligodendroglial apoptosis and axonal survival after traumatic SCI . This unique study includes post mortem spinal cord tissue from 64 cases of SCI and 38 control cases without CNS injury . Each group was subdivided into subgroups of younger and elderly individuals . The results of this study indicate that age at the SCI onset does not adversely affect the cellular inflammatory response to oligodendroglial apoptosis and axonal survival after SCI . These results support the conclusion that elderly individuals have similar neurobiological responses to SCI as younger people and hence treatment decisions should be based on an assessment of the individual patient and not an arbitrary assumption that advanced age should exclude patients with an acute SCI from access to advanced care and translational therapies . | This study examined the potential effects of age on pathobiology of SCI using a unique collection of post mortem spinal cord tissue. Our results indicate that age at the time of injury does not adversely affect the cellular inflammatory response to SCI. Our results also suggest that age at the SCI onset does not influence oligodendroglial apoptosis and axonal survival after SCI. Those results support the conclusion that elderly individuals have similar neurobiological responses to SCI as younger people. |
S0014488620302405 | Closed head traumatic brain injury is a worldwide concern with increasing prevalence and cost to society . Rotational acceleration is a primary mechanism in TBI that results from tissue strains that give rise to diffuse axonal injury . The Closed Head Impact Model of Engineered Rotational Acceleration was recently introduced as a method for the study of impact acceleration effects in pre clinical TBI research . This review provides a survey of the published literature implementing the CHIMERA device and describes pathological imaging neurophysiological and behavioral findings . Findings show CHIMERA inflicts damage in white matter tracts as a key area of injury . Behaviorally repeated studies have shown motor deficits and more chronic cognitive effects after CHIMERA injury . Good progress with model application has been accomplished by investigators attending to what is required for model validation . However the majority of CHIMERA studies only utilize adult male mice . To further establish this model more work with female animals and various age groups need to be performed as well as studies to further establish and standardize methodologies for validation of the models for clinical relevance . Common data elements to standardize the reporting methodology for the CHIMERA literature are suggested . | CHIMERA provides a clinically important rotational acceleration model for brain injuries in mice and and ferrets. There have been 19 published papers primarily using adult male mice with two 0.5 Joule impacts separated by 24 h. CHIMERA studies report robust changes including motor and cognitive deficits and diffuse axonal injury. Further analyses that include females and different aged animals are needed. We outline parameters to standardize the model including common data elements for reporting results. |
S0014488620302429 | Exosomes secreted by microglia have been found to play a role in neurovascular unit injury under the ischemic hypoxic state . However the modulatory effect of exosomes shuttled miRNAs produced by microglia in endothelial cells remains undefined . Here an oxygen glucose deprivation model was constructed both in microglia and brain microvascular endothelial cells . The exosomes secreted by microglia were isolated and the exosomal miRNA profile was detected . Next gain and loss functions of miR 424 5p one of the most differentially expressed miRNAs in microglia derived exosomes were conducted in BMEC . The results demonstrated that exosomes from OGD activated microglia aggravated OGD induced BMEC viability and integrity damage as well as the loss of vascular formation . While the damaging effects were markedly attenuated by inhibiting miR 424 5p . In addition miR 424 5p overexpression significantly aggravated OGD induced BMEC damage and permeability . Mechanistically bioinformatics analysis indicated that miR 424 5p targeted the FGF2 mediated STAT3 signaling pathway which was verified via dual luciferase activity assay and RIP experiment . Furthermore in vivo experiments in the middle cerebral artery occlusion model mice were conducted . The results revealed that inhibition of miR 424 5p markedly reduced neurological dysfunctions and endothelial cell injury induced by MCAO . The above results confirmed that exosomes from OGD activated microglia induced significant cell damage and permeability of BMEC in which the upregulated miR 424 5p in the exosomes functioned by regulating FGF2 STAT3 pathway . | Exosomes from OGD indudced microglia aggravated BMEC injury. Inhibiting miR 424 5p shuttled in the microglial exosomes significantly ameliorated BMEC injury. MiR 424 5p targeted FGF2 and inhibited FGF2mediated STAT3 signaling pathway. Inhibition of miR 424 5p markedly reduced neurological dysfunctions and endothelial cell injury induced by MCAO. |
S0014488620302430 | Follistatin like 1 also named transforming growth factor 1inducible gene is a secreted extracellular glycoprotein expressing widely in nervous system . Several recent studies have revealed that FSTL1 plays an essential role in neurological diseases including neuropathic pain and ischemic stroke . It proves that FSTL1 suppresses synaptic transmission by activating Na K ATPase in DRG neurons and inhibits neuronal apoptosis by phosphorylation AKT signaling . However it is not clear whether FSTL1 can play a role in other type of neuron or neurodegenerative diseases . In this study we found that the mice with | mice exhibit memory deficits and synaptic plasticity impairments. mice exhibit abnormal neural oscillations in the hippocampus. mice exhibit 55 up regulated and 184 down regulated genes in hippocampus. Fstl1 may be a novel target for the neurological diseases with cognitive impairment. |
S0014488620302442 | Parkinson s disease is the second most common neurodegenerative disease . Pharmacotherapy with L DOPA remains the gold standard therapy for PD but is often limited by the development of the common side effect of L DOPA induced dyskinesia which can become debilitating . The only effective treatment for disabling dyskinesia is surgical therapy therefore effective pharmacological treatment of LID is a critical unmet need . Here we show that sub anesthetic doses of ketamine attenuate the development of LID in a rodent model while also having acute anti parkinsonian activity . The long term anti dyskinetic effect is mediated by brain derived neurotrophic factor release in the striatum followed by activation of ERK1 2 and mTOR pathway signaling . This ultimately leads to morphological changes in dendritic spines on striatal medium spiny neurons that correlate with the behavioral effects specifically a reduction in the density of mushroom spines a dendritic spine phenotype that shows a high correlation with LID . These molecular and cellular changes match those occurring in hippocampus and cortex after effective sub anesthetic ketamine treatment in preclinical models of depression and point to common mechanisms underlying the therapeutic efficacy of ketamine for these two disorders . These preclinical mechanistic studies complement current ongoing clinical testing of sub anesthetic ketamine for the treatment of LID by our group and provide further evidence in support of repurposing ketamine to treat individuals with PD . Given its clinically proven therapeutic benefit for both treatment resistant depression and several pain states very common co morbidities in PD sub anesthetic ketamine could provide multiple therapeutic benefits for PD in the future . | Ketamine attenuates the development of L DOPA induced dyskinesia in rodents. Ketamine also has an acute anti parkinsonian activity. The long term effects of ketamine depend on BDNF signaling in the striatum. Maladaptive striatal dendritic mushroom spines are reduced by ketamine. Mushroom spine density in the striatum correlates with the severity of dyskinesia. |
S0014488620302454 | MicroRNAs are powerful regulators of CNS development and diseases . Plasma and cerebrospinal fluid miRs have recently been implicated as potential new sources for biomarker development . Previously we showed that miR 124 3p an essential miR for neuronal identity is highly abundant in neuronal exosomes and its expression decreases in spinal cord of ALS model SOD1G93A mice . In the current study we found a disease associated reduction of miR 124 3p levels specifically in spinal neurons using | miR 124 3p expression levels are decreased in mid staged SOD1G93A spinal motor neurons. Increased extracellular localization of miR 124 3p in lumbar cord in diseased SOD1G93A mice. Increased association between miR 124 3p and neuron derived exosomes in SOD1G93A mice. Positive correlation of CSF miR 124 3p abundance and disease severity in male ALS patients. |
S0014488620302466 | Diabetic peripheral neuropathy is one of the most common complications in diabetic patients . Though the exact mechanism for DPN is unknown it clearly involves metabolic dysfunction and energy failure in multiple cells within the peripheral nervous system . Lactate is an alternate source of metabolic energy that is increasingly recognized for its role in supporting neurons . The primary transporter for lactate in the nervous system monocarboxylate transporter 1 has been shown to be critical for peripheral nerve regeneration and metabolic support to neurons axons . In this study MCT1 was reduced in both sciatic nerve and dorsal root ganglia in wild type mice treated with streptozotocin a common model of type 1 diabetes . Heterozygous MCT1 null mice that developed hyperglycemia following STZ treatment developed a more severe DPN compared to wild type mice as measured by greater axonal demyelination decreased peripheral nerve function and increased numbness to innocuous low threshold mechanical stimulation . Given that MCT1 inhibitors are being developed as both immunosuppressive and chemotherapeutic medications our results suggest that clinical development in patients with diabetes should proceed with caution . Collectively our findings uncover an important role for MCT1 in DPN and provide a potential lead toward developing novel treatments for this currently untreatable disease . | MCT1 is reduced in sciatic nerve and DRG of streptozotocin induced diabetic mice. Reducing MCT1 worsens experimental diabetic neuropathy in mice. Reducing MCT1 led to greater nerve demyelination after induction of diabetes. |
S0014488620302570 | Spinal cord injury often results in devastating effects on function and quality of life . The majority of SCIs occur in the cervical region with restoration of arm and hand function being the highest priority by patients . Current restoration strategies rely on maximizing and optimally redistributing residual muscle functions that remain under volitional control . The polio epidemic and World Wars led to the development and refinement of tendon transfers which has long been the standard reconstructive approach for the upper extremity following SCI . However the past few decades has seen the emergence of nerve transfers from a salvage procedure for the management of peripheral nerve injuries to a powerful reconstructive tool following SCI . Nerve transfers offer distinct advantages over tendon transfers however optimal functional recovery frequently benefits from a multi modality approach and must be tailored to specific injury patterns . Extension of nerve transfers to the lower body presents additional hurdles such as limited donor nerve sources and much longer target distances . | Nerve transfers are a powerful intervention for functional recovery following spinal cord injury. Comparison of nerve versus tendon transfers. Role for nerve transfers in the lower body. Future strategies to enhance nerve transfer approaches. |
S0014488620302582 | The dopamine D2 like receptor agonist ropinirole is often used for early and middle stage Parkinson s disease . However this D2 like agonism based strategy has a complicating problem D2 like agonism may activate D2 autoreceptors on the residual DA neurons in the PD brain potentially inhibiting these residual DA neurons and motor function . We have examined this possibility by using systemic and local drug administration in transcription factor Pitx3 null mutant mice that mimic the DA denervation in early and middle stage PD and in DA neuron tyrosine hydroxylase gene knockout mice that mimic the severe DA loss in late stage PD . We found that in Pitx3Null mice with residual DA neurons and normal mice with normal DA system systemically injected ropinirole inhibited locomotion whereas bilateral dorsal striatal microinjected ropinirole stimulated movement in Pitx3Null mice bilateral microinjection of ropinirole into the ventral tegmental area also inhibited movement in Pitx3Null mice we further determined that ropinirole inhibited nigral DA neuron spike firing in WT mice . In contrast both systemically and striatum locally administered ropinirole increased movements in TH KO mice but produced relatively more dyskinesia than L dopa . Although requiring confirmation in non human primates and PD patients these data suggest that while activating D2 like receptors in striatal projection neurons and hence stimulating movements D2 like agonists can inhibit residual DA neurons and cause akinesia when the residual DA neurons and motor functions are still substantial and this motor inhibitory effect disappears when almost all DA neurons are lost such as in late stage PD . | Ropinirole is often used for early middle stage Parkinson s disease PD . D2 like agonism may activate D2 autoreceptors on the residual dopamine neurons. Systemic ropinirole inhibits motor activity in early middle stage PD mouse model. Striatal ropinirole injection stimulates motor activity in same PD mouse model. Systemic ropinirole stimulates motor activity in late stage PD mouse model. |
S0014488620302594 | Chronic pain is one of the most challenging and debilitating symptoms to manage after traumatic brain injury yet the underlying mechanisms remain elusive . The disruption of normal endogenous pain control mechanisms has been linked to several forms of chronic pain and may play a role in pain after TBI . We hypothesized therefore that dysfunctional descending noradrenergic and serotonergic pain control circuits may contribute to the loss of diffuse noxious inhibitory control a critical endogenous pain control mechanism weeks to months after TBI . For these studies the rat lateral fluid percussion model of mild TBI was used along with a DNIC paradigm involving a capsaicin conditioning stimulus . We observed sustained failure of the DNIC response up to 180 days post injury . We confirmed that descending | DNIC is an endogenous pain control mechanism lost after TBI in rats. Augmenting descending NA signaling via RBX fails to restore DNIC after TBI. Blocking pronociceptive serotonergic signaling after TBI also fails to restore DNIC. Augmenting the serotoninergic inhibitory pain pathway via SSRIs does restore DNIC after TBI. |
S0014488620302624 | Astrocytic Yes associated protein has been implicated in astrocytic proliferation and differentiation in the developing neocortex . However the role of astrocytic YAP in diseases of the nervous system remains poorly understood . Here we hypothesized that astrocytic YAP exerted a neuroprotective effect against cerebral ischemic injury in rats by regulating signal transducer and activator of transcription 3 signaling . In this study we investigated whether the expression of nuclear YAP in the astrocytes of rats increased significantly after middle cerebral artery occlusion and its effect on cerebral ischemic injury . We used XMU MP 1 to trigger localization of YAP into the nucleus and found that XMU MP 1 treatment decreased ischemia stroke induced brain injury including reduced neuronal death and reactive astrogliosis and extenuated release of interleukin 1 interleukin 6 and tumor necrosis factor . Mechanically XMU MP 1 treatment suppressed the expression of phospho STAT3 . We established an in vitro oxygen glucose deprivation reperfusion model to simulate an ischemic condition and further explore the function of astrocytic YAP . We found that nuclear translocation of astrocytic YAP in rats could improve cell vitality decrease the release of inflammatory cytokines and reduce the expression of P STAT3 in vitro . In contrast we also found that inhibition of YAP by verteporfin further aggravated the injury induced by OGD R via STAT3 signaling . In summary our results showed that nuclear localization of astrocytic YAP exerted a neuroprotective effect after cerebral ischemic injury in rats via inhibition of the STAT3 signaling . | There was an increase of nuclear YAP in astrocytes instead of neurons and microglia in response to ischemia stroke. Astrocytic nuclear YAP was involved in cerebral ischemia reperfusion injury. Nuclear localization of astrocytic YAP exerted a neuroprotective effect via inhibition of the STAT3 signaling. YAP is a promising therapeutic target with protective effects against ischemia stroke. |
S0014488620302636 | mutations cause Tuberous Sclerosis Complex and lead to mechanistic target of rapamycin hyperactivation evidenced by hyperphosphorylation of ribosomal S6 protein and 4 elongation factor binding protein 1 . Amino acid levels modulate mTOR dependent S6 and 4E BP1 phosphorylation in non neural cells but this has not been comprehensively investigated in neurons . The effects of AA levels on mTOR signaling and S6 and 4E BP1 phosphorylation were analyzed in | TSC is highly associated with epilepsy and autism caused by mutations in. or. mTOR pathway hyperactivation is abolished by amino acid deprivation in. KO cells. mTOR pathway hyperactivation is not abolished by amino acid deprivation in. KO cells. Response of mTOR signaling to nutrients may have relevance for clinical therapeutics. |
S0014488620302648 | GABAergic neurons in the rostromedial tegmental nucleus receive major input from the lateral habenula which conveys negative reward and motivation related information and project intensively to midbrain dopamine neurons including those in the ventral tegmental area and substantia nigra pars compacta . The RMTg VTA circuit has been shown to be linked to the affective behavior but the role of the RMTg SNc circuit in aversion and depression has not been well understood . This study demonstrated that exciting or inhibiting Vgat | The activation of the RMTg SNc pathway caused aversive and despair behavior. Activating the pathway inhibited firing rates of SNc putative dopamine neurons. Inhibiting the circuit reversed behavior despair in CRS depression model. |
S001448862030265X | Sigma 1 receptors have been implicated in many neurological and psychiatric disorders and are a novel target for the treatment of such disorders . Sig 1R expression activity deficits are linked to neurodegeneration whereas the mechanisms mediated by Sig 1R are still unclear . Here presynaptic | Sigma 1R antagonist NE 100 has biphasic effects on synaptosomal GABA uptake. NE 100 mitigates hypoxia associated transporter mediated glutamate release. NE 100 decreases synaptosomal KCl evoked exocytotic release of GABA glutamate. Ionomycin stimulated release of GABA glutamate is not affected by NE 100. Therefore NE 100 specifically acts in an acute manner at the presynaptic level |
S0014488620302673 | Despite the ability of peripheral nerves to regenerate after injury failure occurs due to an inability of supporting cells to maintain growth resulting in long term consequences such as sensorimotor dysfunction and neuropathic pain . Here we investigate the potential of engaging the cellular adaptive response to hypoxia via inhibiting its negative regulators to enhance the regenerative process . Under normoxic conditions prolyl hydroxylase domain proteins 1 2 and 3 hydroxylate the key metabolic regulator hypoxia inducible factor 1 marking it for subsequent proteasomal degradation . We inhibited PHD protein function systemically via either individual genetic deletion or pharmacological pan PHD inhibition using dimethyloxalylglycine . We show enhanced axonal regeneration after sciatic nerve crush injury in PHD1 | Mimicking the hypoxia response accelerates functional nerve regeneration. Hypoxia mimicry attenuates neuropathic pain following nerve injury. Deleting hypoxia response inhibitors protects denervated muscle fibres from atrophy. Altered macrophage polarization may account for hypoxiamimetic effects. |
S0014488620302697 | Peripheral nerve injuries can significantly reduce quality of life . While some recover most do not recover fully resulting in neuropathic pain and loss of sensation and motor function . Research on the mechanisms of peripheral nerve regeneration could elucidate poor patient outcomes and potential treatments . This study was designed to determine if brain derived neurotrophic factor is necessary for pudendal nerve regeneration and functional recovery . Peripheral administration of tyrosine kinase B functional chimera was used to inhibit the BDNF regenerative pathway . Female Sprague Dawley rats received tyrosine kinase B functional chimera or saline after a pudendal nerve crush or Sham PNC and were divided into three groups Sham PNC PNC Saline and PNC TrkB . Seven days after injury relative | Brain derived neurotrophic factor is needed for pudendal nerve regeneration. TrkB Fc decreases peripheral free brain derived neurotrophic factor. TrkB Fc administration decreases PN motoneuron beta II tubulin expression. |
S0014488620302739 | Hypoxic ischemic brain injury is one of the most common neurological problems occurring in premature and full term infants after perinatal complications . Hypothermia is the only treatment approved for HI encephalopathy in newborns . However this treatment is only partially protective can not be used to treat premature infants and has limited efficacy to treat severe HI encephalopathy . Inflammation contributes to the evolution of HI brain injury in neonates . Inter alpha Inhibitor Proteins are immunomodulatory proteins that have neuroprotective properties after exposure to moderate HI in neonatal rats . The objective of the current study was to determine the neuroprotective efficacy of treatment with IAIPs starting immediately after or with a delay of one hour after exposure to severe HI of 120min duration . One hundred and forty six 7 day old rat pups were randomized to sham control HI and immediate treatment with IAIPs or placebo and sham HI and delayed treatment with IAIPs or PL . IAIPs or PL were given at zero 24 and 48h after HI or 1 24 and 48h after HI . Total brain infarct volume was determined 72h after exposure to HI . Treatment with IAIPs immediately after HI decreased | Exogenous inter alpha inhibitor proteins IAIPs reduce severe hypoxic ischemic injury. Exogenous IAIPs decrease hypoxic ischemic infarction volumes in males and females. IAIP treatment after a 1h reduces hypoxic ischemic infarction volumes in male rats. |
S0014488620302855 | Individuals with demyelinating diseases often experience difficulties during social interactions that are not well studied in preclinical models . Here we describe a novel juvenile focal corpus callosum demyelination murine model exhibiting a social interaction deficit . Using this preclinical murine demyelination model we discover that application of metformin an FDA approved drug in this model promotes oligodendrocyte regeneration and remyelination and improves the social interaction . This beneficial effect of metformin acts through stimulating Ser436 phosphorylation in CBP a histone acetyltransferase . In addition we found that metformin acts through two distinct molecular pathways to enhance oligodendrocyte precursor proliferation and differentiation respectively . Metformin enhances OPC proliferation through early stage autophagy inhibition while metformin promotes OPC differentiation into mature oligodendrocytes through activating CBP Ser436 phosphorylation . In summary we identify that metformin is a promising remyelinating agent to improve juvenile demyelination associated social interaction deficits by promoting oligodendrocyte regeneration and remyelination . | A focal corpus callosum demyelination model exhibits a social interaction deficit. Metformin reverses the social interaction deficit caused by focal demyelination. Metformin promotes white matter remyelination following focal demyelination. Metformin promotes oligodendrocyte regeneration through phosphorylating CBP Ser436. Metformin acts on two distinct pathways to promote OPC proliferation and differentiation. |
S0014488620302892 | Chemotherapy induced peripheral neurotoxicity represents one of the most relevant dose limiting side effects that can affect cancer patients treated with the common antineoplastic agents . Since the severity of neurotoxicity often leads to dose reduction or early cessation of chemotherapy the investigation of molecular mechanisms underlying chemotherapy induced peripheral neurotoxicity is an urgent clinical need in order to better understand its physiopathology and find effective strategies for neuroprotection . Several in vivo preclinical models of chemotherapy induced peripheral neurotoxicity have been developed but a great variability in mouse strain dose route of administration of the drug treatment schedule and assessment of neurotoxicity is observed between the different published studies making difficult the comparison and interpretation of their results . In many of these studies only behavioural tests are used as outcome measures while possible neurophysiological and neuropathological changes are not evaluated . | Different mouse models of oxaliplatin induced peripheral neurotoxicity are described. Great variability exists among different mouse models. Evaluation of the results are often limited to behavioural tests. Multimodal assessment increases the reliability of animal models. Animal models and investigation methods should be standardized between workgroups. |
S0014488620302909 | Ketamine has been reported to exert a prophylactic effect against stress induced depressive like behavior by modulating the guanosine based purinergic system . However the molecular pathways underlying its prophylactic effect and whether guanosine also elicits a similar effect remain to be determined . Here we investigated the prophylactic effect of ketamine and guanosine against corticosterone induced depressive like behavior in mice . Furthermore we characterized if the prophylactic response may be associated with mTORC1 driven signaling in the hippocampus and prefrontal cortex . A single administration of ketamine but not guanosine given 1week before the pharmacological stress prevented CORT induced depressive like behavior in the tail suspension test and splash test . Fluoxetine treatment for 3weeks did not prevent CORT induced behavioral effects . A single administration of subthreshold doses of ketamine plus guanosine partially prevented the CORT induced depressive like behavior in the SPT . Additionally CORT reduced Akt Ser | CORT induces depressive like behavior and hippocampal synaptogenic markers deficits. Ketamine prevents CORT induced behavioral and hippocampal synaptogenic alterations. Guanosine or fluoxetine are unable to prevent the alterations induced by CORT. Ketamine plus guanosine partially prevent CORT induced reduced self care behavior. |
S0014488620302910 | Selective elimination of respiratory motor neurons using intrapleural injections of cholera toxin B fragment conjugated to saporin mimics motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases . This CTB SAP model allows us to study the impact of motor neuron death on the output of surviving phrenic motor neurons . After 7 days of CTB SAP phrenic long term facilitation is enhanced but returns towards control levels at 28d . However the mechanism responsible for this difference in magnitude of pLTF is unknown . In nave rats pLTF predominately requires 5 HT2 receptors the new synthesis of BDNF and MEK ERK signaling however pLTF can alternatively be induced via A | Phrenic motor neuron loss induces shifts in signaling mechanisms for pLTF. pLTF observed in 7d CTB SAP treated rats requires the new synthesis of TrkB. Both PI3K Akt and MEK ERK signaling contribute to pLTF in 7d CTB SAP rats. pLTF is elicited through BDNF and MEK ERK signaling in 28d CTB SAP rats. |
S0014488620302922 | We investigated whether type 2 diabetes mellitus a risk factor of stroke affects the level of scavenger receptor CD36 and the uptake of its ligand oxidized LDL and whether pioglitazone a drug that enhances CD36 promotes oxLDL uptake . Compared to normoglycemic db mice adult db db mice showed a pronounced reduction in surface CD36 expression on myeloid cells from the blood brain and bone marrow as detected by flow cytometry which correlated with elevated plasma soluble CD36 as determined by ELISA . Increased CD36 expression was found in brain macrophages and microglia of both genotypes 7days after ischemic stroke . In juvenile db db mice prior to obesity and hyperglycemia only a mild reduction of surface CD36 was found in blood neutrophils while all other myeloid cells showed no difference relative to the db strain . In vivo oral pioglitazone treatment for four weeks increased CD36 levels on myeloid cells in db db mice . In vitro uptake of oxLDL by bone marrow derived macrophages of db db mice was reduced relative to db mice in normal glucose medium . OxLDL uptake inversely correlated with glucose levels in the medium in db BMDMs . Furthermore pioglitazone restored oxLDL uptake by BMDMs from db db mice cultured in high glucose . Our data suggest that T2DM is associated with reduced CD36 on adult myeloid cells and pioglitazone enhances CD36 expression in db db cells . T2DM or high glucose reduces oxLDL uptake while pioglitazone enhances oxLDL uptake . Our findings provide new insight into the mechanism by which pioglitazone may be beneficial in the treatment of insulin resistance . | CD36 levels markedly reduced in myeloid cells of the adult but not of juvenile T2DM mice. Soluble CD36 levels increased in the adult T2DM mice. T2DM or high glucose impairs uptake of oxLDL in BMDM cells. Pioglitazone enhances CD36 levels in diabetic cells and oxLDL uptake. |
S0014488620302934 | Traumatic brain injury has been regarded as one of the leading cause of injury related death and disability . White matter injury after TBI is characterized by axon damage and demyelination resulting in neural network impairment and neurological deficit . Brain derived neurotrophic factor can promote white matter repair . The activation of peroxisome proliferatoractivated receptor gamma has been reported to promote microglia macrophages towards anti inflammatory state and therefore to promote axon regeneration . Bexarotene an agonist of retinoid X receptor can activate RXR PPAR heterodimers . The aim of the present study was to identify the effect of bexarotene on BDNF in microglia macrophages and axon sprouting after TBI in mice . Bexarotene was administered intraperitoneally in C57BL 6 mice undergoing controlled cortical impact . PPAR dependency was determined by intraperitoneal administration of a PPAR antagonist T0070907 . We found that bexarotene promoted axon regeneration indicated by increased growth associated protein 43 expression myelin basic protein expression and biotinylated dextran amine | Bexarotene promotes axon sprouting after traumatic brain injury in mice. Bexarotene increases microglia macrophages specific brain derived neuroptrophic factor expression after traumatic brain injury. Bexarotene promotes microglia towards anti iflammatory state after traumatic brain injury in mice. |
S0014488620302958 | Neuroinflammation is one of the most common etiology in various neurological disorders and responsible for multi array neurotoxic manifestations such as neurodegeneration neurotransmitters alteration and cognitive dysfunction . NR is a natural bioactive molecule which possesses significant antioxidant and anti inflammatory potential but suffers from glitches of low solubility low bioavailability and fast hepatic metabolism . In the current study we fabricated nano engineered lipid carrier of nerolidol for its effective delivery into the brain and explored its effect on neuroinflammation neurotransmitters level and on dysfunctional behavioral attributes induced by CYC . The binding affinity of nerolidol with NLRP3 and TLR 4 was performed which showed stong interaction between them . NR NLC was prepared by the ultrasonication methods and particle size was determined by Zeta sizer . Swiss Albino mice were divided into 5 groups | Cyclophosphamide 200mg kg i.p. induced significant neurotoxicity. in hippocampus and cortex of Swiss Albino mice. Nerolidol nanoformulation NR NLC 200 and nerolidol suspension NR 200 at the dose of 200mg kg p.o. were evaluated for neuroprotective effect. Molecular docking study revealed potential interaction profile of nerolidol in the binding pockets of NLRP3 and TLR 4. NR NLC 200 was found effective in reversing CP induced neurotoxic manifestations in these mice. |
S001448862030296X | Activation of amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid receptors increases phrenic motor output . Ampakines are a class of drugs that are positive allosteric modulators of AMPA receptors . We hypothesized that 1 ampakines can stimulate phrenic activity after incomplete cervical spinal cord injury and 2 pairing ampakines with brief hypoxia could enable sustained facilitation of phrenic bursting . Phrenic activity was recorded ipsilateral and contralateral to C2 spinal cord hemisection in anesthetized adult rats . Two weeks after C2Hx ampakine CX717 increased IL and CL burst amplitude in 8 of 8 rats . After 90min IL and CL bursting remained above baseline in 7 of 8 rats . Pairing ampakine with a single bout of acute hypoxia 5 min arterial partial pressure of O | Cervical spinal cord injury cSCI impairs phrenic motor output PMO . Ampakines are positive allosteric modulators of AMPA receptors. Ampakine CX717 increased bilateral PMO at 2 and 8weeks post cSCI. Ampakines may help restore respiratory muscle activation after cSCI. |
S0014488620302971 | Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types to turn senescent under neurodegenerative conditions . Senescent astrocytes were detected in Parkinson s disease patients brains besides reactive astrocytes yet the difference between senescent and reactive astrocytes is unclear . We aimed to characterize senescent astrocytes in comparison to reactive astrocytes and investigate differences and similarities . In a cell culture model of human fetal astrocytes we determined a unique senescent transcriptome distinct from reactive astrocytes which comprises dysregulated pathways . Both senescent and reactive human astrocytes activated a proinflammatory pattern . Astrocyte senescence was at least partially depending on active mechanistic target of rapamycin and DNA damage response signaling both drivers of senescence . To further investigate how PD and senescence connect to each other we asked if a PD linked environmental factor induces senescence and if senescence impairs midbrain neurons . We could show that the PD linked pesticide rotenone causes astrocyte senescence . We further delineate that the senescent secretome exaggerates rotenone induced neurodegeneration in midbrain neurons differentiated from human induced pluripotent stem cells of PD patients with alpha synuclein gene | Senescent astrocytes express a unique transcriptome pattern. A proinflammatory state is activated in both senescent and reactive astrocytes. Stress induced senescence in astrocytes depends at least in part on active mTOR and DDR signaling. The PD linked pesticide rotenone induces astrocyte senescence. Human. duplication neurons exhibit a rotenone dependent vulnerability to senescent stimuli. |
S0014488620302995 | A major portion of individuals affected by traumatic spinal cord injury experience one or more types of chronic neuropathic pain which is often intractable to currently available treatments . The availability of reliable behavioral assays in pre clinical models of SCI induced NP is therefore critical to assess the efficacy of new potential therapies . Commonly used assays to evaluate NP related behavior in rodents such as Hargreaves thermal and von Frey mechanical testing rely on the withdrawal response to an evoked stimulus . However other assays that test spontaneous non evoked NP related behavior or supraspinal aspects of NP would be highly useful for a more comprehensive assessment of NP following SCI . The Mouse Grimace Scale is a tool to assess spontaneous supraspinal pain like behaviors in mice however the assay has not been characterized in a mouse model of SCI induced chronic NP despite the critical importance of mouse genetics as an experimental tool . We found that beginning 2weeks after cervical contusion SCI mice exhibited increased facial grimace features compared to laminectomy only control mice and this grimace phenotype persisted to the chronic time point of 5weeks post injury . We also found a significant relationship between facial grimace score and the evoked forepaw withdrawal response in both the Hargreaves and von Frey tests at 5weeks post injury when both laminectomy only and SCI mice were included in the analysis . However within only the SCI group there was no correlation between grimace score and Hargreaves or von Frey responses . These results indicate both that facial grimace analysis can be used as an assay of spontaneous NP related behavior in the mouse model of SCI and that the information provided by the MGS may be different than that provided by evoked tests of sensory function . | Cervical spinal cord injury mice exhibit increased facial grimace features. Grimace testing can be used to assess spontaneous neuropathic pain in SCI mice. |
S0014488620303125 | Retinal ganglion cell death causes irreversible blindness in adult mammals . Death of RGC occurs in diseases including glaucoma or injuries to the optic nerve . To investigate mechanisms involved in RGC degeneration we evaluated the phosphoproteomic changes in the retina induced by ON injury . Intraorbital optic nerve crush was performed in adult C57BL 6J mice . Retinas were collected at 0 6 and 12h following ONC . Retinal proteins labeled with CyDye C2 were subject to 2D PAGE followed by phosphoprotein staining and in gel cross gel image analysis . Proteins with significant changes in phosphorylation in retinas of the injured eyes compared to the control eyes were spot picked tryptic digested and peptide fragments were analyzed by MALDI TOF and TOF TOF . Intraorbital ONC increased phosphorylation of many retinal proteins . Among them 29 significantly phosphorylated proteins were identified . PANTHER analysis showed that these proteins are associated with a variety of protein classes cellular components biological processes and signaling pathways . One of the identified proteins phosphoprotein enriched in astrocytes 15 was further validated by western blotting and immunofluorescence staining . Functions of PEA15 were determined in cultured astrocytes . PEA15 knockdown reduced astrocyte phagocytic activity but promoted cell migration . Long term PEA15 knockdown also decreased astrocyte ATP level . This study provides new insights into mechanisms of RGC degeneration after ON injury as well as central nervous system neurodegeneration since the retina is an extension of the CNS . These new insights will lead to novel therapeutic targets for retinal and CNS neurodegeneration . | Intraorbital optic nerve crush affected retinal protein phosphorylation. A variety of proteins cellular components processes and pathways were activated. Phosphoprotein PEA15 may regulate astrocyte reactivity induced by optic nerve injury. |
S0014488620303137 | Wnt5b a member of Wnt family plays multiple roles in tumor progression and metastasis . However whether Wnt5b contributes to the sensitization of dorsal root ganglia neurons and pathogenesis of bone cancer pain still remains unclear . Here we found that the protein expression of Wnt5b and its atypical tyrosine protein kinase receptor Ryk was upregulated in ipsilateral DRGs in tumor bearing mice . Application of Wnt5b evoked an increased discharge frequency in isolated DRG neurons and pain hypersensitivity in nave mice which were almost completely prevented by anti Ryk antibody . Moreover intrathecal injection of anti Ryk antibody to tumor bearing mice significantly inhibited bone cancer induced mechanic allodynia and thermal hyperalgesia . Subsequently we also demonstrated that application of Wnt5b to cultured DRG neurons could enhance membrane P2X3 receptors and meATP induced currents . Intrathecal injection of calmodulin dependent protein kinase II inhibitor KN93 or P2X3 receptors antagonist A317491 almost completely abolished Wnt5b induced mechanical allodynia and thermal hyperalgesia in mice . Meanwhile pretreatment with anti Ryk antibody or CaMKII inhibitor KN93 can attenuate bone cancer induced the upregulation of P2X3 membrane protein as well as pain hypersensitivity . These findings suggested that Wnt5b Ryk promoted the trafficking of P2X3 receptors to the membrane via the activation of CaMKII in primary sensory neurons resulting in peripheral sensitization and bone cancer induced pain . Our results may offer a potential therapeutic strategy for bone cancer pain . | Wnt5b Ryk signal participates in the development of bone cancer pain. Wnt5b enhances the firing discharge frequency of small diameter DRG neurons. Wnt5b induces the functional upregulation of P2X3 receptors in DRG neurons. |
S0014488620303150 | Vasospasm and delayed cerebral ischemia contribute significantly to the morbidity mortality associated with aneurysmal subarachnoid hemorrhage . While considerable research effort has focused on preventing or reversing vasospasm SAH induced brain injury occurs in response to a multitude of concomitantly acting pathophysiologic mechanisms . In this regard the pleiotropic epigenetic responses to conditioning based therapeutics may provide an ideal SAH therapeutic strategy . We previously documented the ability of hypoxic preconditioning to attenuate vasospasm and neurological deficits after SAH in a manner that depends on the activity of endothelial nitric oxide synthase . The present study was undertaken to elucidate whether the NAD dependent protein deacetylase sirtuin isoform SIRT1 is an upstream mediator of hypoxic PC induced protection and to assess the efficacy of the SIRT1 activating polyphenol Resveratrol as a pharmacologic preconditioning therapy . Wild type C57BL 6J mice were utilized in the study and subjected to normoxia or hypoxic PC . Surgical procedures included induction of SAH via endovascular perforation or sham surgery . Multiple endpoints were assessed including cerebral vasospasm neurobehavioral deficits SIRT1 expression via quantitative real time PCR for mRNA and western blot for protein quantification . Pharmacological agents utilized in the study include EX 527 and Resveratrol . Hypoxic PC leads to rapid and sustained increase in cerebral SIRT1 mRNA and protein expression . SIRT1 inhibition blocks the protective effects of hypoxic PC on vasospasm and neurological deficits . Resveratrol pretreatment dose dependently abrogates vasospasm and attenuates neurological deficits following SAH beneficial effects that were similarly blocked by pharmacologic inhibition of SIRT1 . SIRT1 mediates hypoxic preconditioning induced protection against neurovascular dysfunction after SAH . Resveratrol mimics this neurovascular protection at least in part via SIRT1 . Activation of SIRT1 is a promising novel pleiotropic therapeutic strategy to combat DCI after SAH . | Hypoxic preconditioning protects against deficits after subarachnoid hemorrhage. Hypoxic preconditioning induces robust upregulation of SIRT1. SIRT1 mediates hypoxic preconditioning induced protection in subarachnoid hemorrhage. Resveratrol mimics preconditioning induced protection in subarachnoid hemorrhage. |
S0014488620303216 | Alzheimer s disease and type 2 diabetes mellitus have a common pathology . Both diseases are characterized by local deposition of amyloid proteins in the brain or islet organ but their phenotypes and clinical manifestation vary widely . Although the sources of islet amyloid polypeptide and amyloid beta are independent their fibrillar sequences are highly homologous . The prevalence of AD in T2DM populations is considerably higher than that in the normal population but a mechanistic linkage remains elusive . Therefore the present study aimed to explore the effects of A42 deposition in the brain on the persistently expression of human IAPP . Additionally cognitive ability synaptic plasticity the state of neural stem cells and mitochondrial function were evaluated at 2 or 6months after stereotaxically injected the oligomer A | hIAPP generated from pancreatic islet deposits in hippocampus of hIAPP transgenic mice. Exogenous A. interacted with hIAPP in hippocampus and aggravated the amyloid deposition with aging in hIAPP transgenic mice. Interaction of A. and hIAPP reduced synapse and adult stem cells in hippocampus. Interaction of A. and hIAPP caused dysfunction of mitochondrial in vivo and in vitro. |
S001448862030323X | Women with catamenial epilepsy often experience increased seizure burden near the time of ovulation or menstruation . To date a rodent model of chronic temporal lobe epilepsy that exhibits similar endogenous fluctuations in seizures has not been identified . Here we investigated whether seizure burden changes with the estrous cycle in the intrahippocampal kainic acid mouse model of TLE . Adult female IHKA mice and saline injected controls were implanted with EEG electrodes in the ipsilateral hippocampus . At one and two months post injection 24 7 video EEG recordings were collected and estrous cycle stage was assessed daily . Seizures were detected using a custom convolutional neural network machine learning process . Seizure burden was compared within each mouse between diestrus and combined proestrus and estrus days at two months post injection . IHKA mice showed higher seizure burden on pro estrus compared with diestrus characterized by increased time in seizures and longer seizure duration . When all IHKA mice were included no group differences were observed in seizure frequency or EEG power . However increased baseline seizure burden on diestrus was correlated with larger cycle associated differences and when analyses were restricted to mice that showed the severe epilepsy typical of the IHKA model increased seizure frequency on pro estrus was also revealed . Controls showed no differences in EEG parameters with cycle stage . These results suggest that the stages of proestrus and estrus are associated with higher seizure burden in IHKA mice . The IHKA model may thus recapitulate at least some aspects of reproductive cycle associated seizure clustering . | Convolutional neural network machine learning method detects seizures in mice. IHKA female mice show increased seizure burden on proestrus and estrus. Higher seizure burden on diestrus correlated with larger cycle associated differences. IHKA mouse model may be useful in modeling catamenial like seizure exacerbation. |
S0021961418309200 | The paper presents the results of the Pb Sb Bi ternary system thermodynamic study . Experimental data were obtained using the EMF method in the temperature range from 873 to 973K . The alloys compositions related to the concentration triangle projections with ratios of antimony and bismuth mole fractions | The equilibrium potentials of Pb Sb Bi alloys in the KCl PbCl2 50 50mol melt were measured. The integral properties of the Pb Sb Bi system were calculated. The excess integral functions and integral enthalpy are illustrated in the concentration triangle. The values of excess integral Gibbs energy and entropy are found. |
S0021961418311698 | In continuation to our prior investigational studies on the interactions between binary mixtures of alkoxy alkanols and alcohols here we report density speed of sound FT IR as well as NMR analysis of 2 ethanol CH | Binary mixtures of 2 2 butoxyethoxy ethanol with alcohols have been studied at different temperatures. Strong H bonding interactions between the components are confirmed that decreases with increasing chain length of alcohols. FT IR and NMR studies strongly corroborate the experimental and computational analysis results. |
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