LRRC8A-dependent volume-regulated anion channels contribute to ischemia-induced brain injury and glutamatergic input to hippocampal neurons.
Abstract Volume-regulated anion channels (VRACs) are critically involved in regulating cell volume, and leucine-rich repeat-containing protein 8A (LRRC8A, SWELL1) 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 Lrrc8a conditional knockout (Lrrc8a-cKO) mice produced by crossing NestinCre+/- with Lrrc8aflox+/+ mice died 7-8 weeks of age, indicating an essential role of brain LRRC8A for survival. Middle cerebral artery occlusion (MCAO) caused an early increa...
Source: Experimental Neurology - June 26, 2020 Category: Neurology Authors: Zhou JJ, Luo Y, Chen SR, Shao JY, Sah R, Pan HL Tags: Exp Neurol Source Type: research

Activated WNK3 induced by intracerebral hemorrhage deteriorates brain injury maybe via WNK3/SPAK/NKCC1 pathway.
CONCLUSIONS: 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 in vivo and in vitro. Thus, WNK3 and WNK3/SPAK/NKCC1 signaling pathway are potential targets for treating SBI after ICH. PMID: 32589890 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 23, 2020 Category: Neurology Authors: Wu D, Lai N, Deng R, Liang T, Pan P, Yuan G, Li X, Li H, Shen H, Wang Z, Chen G Tags: Exp Neurol Source Type: research

Aged heterozygous Cdkl5 mutant mice exhibit spontaneous epileptic spasms.
Abstract CDKL5 deficiency disorder (CDD) 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 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...
Source: Experimental Neurology - June 22, 2020 Category: Neurology Authors: Mulcahey PJ, Tang S, Takano H, White A, Davila Portillo DR, Kane OM, Marsh ED, Zhou Z, Coulter DA Tags: Exp Neurol Source Type: research

Sex differences in stroke co-morbidities.
Abstract Males and females possess distinct biological differences that manifest in diverse risk profiles for acute and chronic diseases. A well-documented example of this is ischemic stroke. It has been demonstrated that older females have greater prevalence of, and worse outcome after, ischemic stroke than do males and younger females. Loss of estrogen after menopause is heavily implicated as a contributing factor for this phenomenon; however, there is mounting evidence to suggest that certain risk factors tend to occur more often in older females, such as hypertension and atrial fibrillation, while others more ...
Source: Experimental Neurology - June 22, 2020 Category: Neurology Authors: Branyan TE, Sohrabji F Tags: Exp Neurol Source Type: research

A novel pyrazolo [3,4-d] pyrimidine, KKC080106, activates the Nrf2 pathway and protects nigral dopaminergic neurons.
Abstract The transcription factor nuclear factor-erythroid 2-related factor-2 (Nrf2) 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-d] pyrimidine derivatives and discovered a novel, non-electrophilic compound: 1-ben...
Source: Experimental Neurology - June 21, 2020 Category: Neurology Authors: Lee JA, Kim HR, Son HJ, Shin N, Han SH, Chung CS, Kim DJ, Hwang O Tags: Exp Neurol Source Type: research

MicroRNA-153 impairs hippocampal synaptic vesicle trafficking via downregulation of synapsin I in rats following chronic cerebral hypoperfusion.
Abstract Chronic cerebral hypoperfusion (CCH) 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 (DRE) phase in CA3-CA1 circuit and decreased synapsin I in CCH rats suffering from bilateral common carotid artery occlusion (2VO). Further study showed an upregulated miR-153 in the hippocampus of 2VO rats. In vitro, overexpression of miR-153 downregulated synapsin I...
Source: Experimental Neurology - June 21, 2020 Category: Neurology Authors: Zhang S, Yan ML, Yang L, An XB, Zhao HM, Xia SN, Jin Z, Huang SY, Qu Y, Ai J Tags: Exp Neurol Source Type: research

Targeting the blood-nerve barrier for the management of immune-mediated peripheral neuropathies.
Abstract Healthy peripheral nerves encounter, with increased frequency, numerous chemical, biological, and biomechanical forces. Over time and with increasing age, these forces collectively contribute to the pathophysiology of a spectrum of traumatic, metabolic, and/or immune-mediated peripheral nerve disorders. The blood-nerve barrier (BNB) serves as a critical first-line defense against chemical and biologic insults while biomechanical forces are continuously buffered by a dense array of longitudinally orientated epineural collagen fibers exhibiting high-tensile strength. As emphasized throughout this Experiment...
Source: Experimental Neurology - June 17, 2020 Category: Neurology Authors: Stubbs EB Tags: Exp Neurol Source Type: research

Bilateral cervical contusion spinal cord injury: A mouse model to evaluate sensorimotor function.
Abstract 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 clin...
Source: Experimental Neurology - June 16, 2020 Category: Neurology Authors: Reinhardt D, Stehlik K, Satkunendrarajah K, Kroner A Tags: Exp Neurol Source Type: research

Emerging role of microRNAs in ischemic stroke with comorbidities.
Abstract Ischemic stroke is one of the major causes of global disability and death. Comorbidities in stroke are not only risk factors for an increased incidence of stroke, but also adversely impact stroke outcome. Stroke patients with co-morbidities have worse deficit, long term disability and high mortality rate and extended hospitalization stay. MicroRNAs (miRNAs) are noncoding RNA molecules, and are emerging as key molecular mediators of ischemic stroke and other diseases. Thus, focusing on the treatment of stroke and its comorbidities with miRNAs appears to be particularly important. In this review article, we...
Source: Experimental Neurology - June 16, 2020 Category: Neurology Authors: Qian Y, Chopp M, Chen J Tags: Exp Neurol Source Type: research

PLPP/CIN-mediated Mdm2 dephosphorylation increases seizure susceptibility via abrogating PSD95 ubiquitination.
Abstract In the brain, murine double minute-2 (Mdm2), an E3-ubiquitin ligase, modulates neuronal excitability by regulating glutamate receptor and postsynaptic density 95 (PSD95) levels through ubiquitination. Thus, Mdm2 is relevant to epileptic seizures in human patients. Although phosphorylation at serine (S) 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 (PLPP/CIN) in Mdm2 dephosphorylation that may negatively regulate PSD95 ubiquitination. As compared to wild-type mice, PLPP/CIN knoc...
Source: Experimental Neurology - June 16, 2020 Category: Neurology Authors: Kim JE, Lee DS, Kim TH, Park H, Kim MJ, Kang TC Tags: Exp Neurol Source Type: research

Blast exposure predisposes the brain to increased neurological deficits in a model of blast plus blunt traumatic brain injury.
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 ...
Source: Experimental Neurology - June 15, 2020 Category: Neurology Authors: Aravind A, Kosty J, Chandra N, Pfister BJ Tags: Exp Neurol Source Type: research

TTDA inhibited apoptosis by regulating the p53-Bax/Bcl2 axis in glioma.
Abstract The trichothiodystrophy group A protein (TTDA) 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. ...
Source: Experimental Neurology - June 12, 2020 Category: Neurology Authors: Bai HL, Kang CM, Sun ZQ, Li XH, Dai XY, Huang RY, Zhao JJ, Bei YR, Huang XZ, Lu ZF, Wu SG, Lu JB, Ping BH, Wang Q, Hu YW Tags: Exp Neurol Source Type: research

Cellular and molecular features of neurogenic skeletal muscle atrophy.
e A Abstract Neurogenic atrophy refers to the loss of muscle mass and function that results directly from injury or disease of the peripheral nervous system. Individuals with neurogenic atrophy may experience reduced functional status and quality of life and, in some circumstances, reduced survival. Distinct pathological findings on muscle histology can aid in diagnosis of a neurogenic cause for muscle dysfunction, and provide indicators for the chronicity of denervation. Denervation induces pleiotypic responses in skeletal muscle, and the molecular mechanisms underlying neurogenic muscle atrophy appear to share c...
Source: Experimental Neurology - June 10, 2020 Category: Neurology Authors: Ehmsen JT, Höke A Tags: Exp Neurol Source Type: research

Diminished enteric neuromuscular transmission in the distal colon following experimental spinal cord injury.
Abstract Neurogenic bowel following spinal cord injury (SCI) 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 (EJPs and IJPs, respectively) in the distal colon of rats. We previousl...
Source: Experimental Neurology - June 8, 2020 Category: Neurology Authors: White AR, Werner CM, Holmes GM Tags: Exp Neurol Source Type: research

Chronic defects in intraspinal mechanisms of spike encoding by spinal motoneurons following chemotherapy.
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 5 weeks 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...
Source: Experimental Neurology - June 5, 2020 Category: Neurology Authors: Housley SN, Nardelli P, Powers RK, Rich MM, Cope TC Tags: Exp Neurol Source Type: research

Mechano growth factor interacts with nucleolin to protect against cisplatin-induced neurotoxicity.
Abstract Mechano growth factor (MGF) is an alternatively spliced form of insulin-like growth factor-1 (IGF-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 30-40% of treated patients. Our studies were designed to see if MGF would protect dorsal root ganglion (DRG) neurons from cisplatin-induced neurotoxicity and to identify potential mechanisms that may be involved. Expres...
Source: Experimental Neurology - June 5, 2020 Category: Neurology Authors: Podratz JL, Tang JJ, Polzin MJ, Schmeichel AM, Nesbitt JJ, Windebank AJ, Madigan NN Tags: Exp Neurol Source Type: research

A novel fast-channel myasthenia caused by mutation in β subunit of AChR reveals subunit-specific contribution of the intracellular M1-M2 linker to channel gating.
A novel fast-channel myasthenia caused by mutation in β subunit of AChR reveals subunit-specific contribution of the intracellular M1-M2 linker to channel gating. Exp Neurol. 2020 Jun 03;:113375 Authors: Shen XM, Di L, Shen S, Zhao Y, Neumeyer AM, Selcen D, Sine SM, Engel AG Abstract Abstarct Genetic variants causing the fast-channel congenital myasthenic syndrome (CMS) have been identified in the α, δ, and ε but not the β subunit of acetylcholine receptor (AChR). A 16-year-old girl with severe myasthenia had low-amplitude and fast-decaying miniature endplate potentials. ...
Source: Experimental Neurology - June 3, 2020 Category: Neurology Authors: Shen XM, Di L, Shen S, Zhao Y, Neumeyer AM, Selcen D, Sine SM, Engel AG Tags: Exp Neurol Source Type: research

Traumatic brain injury and hippocampal neurogenesis: Functional implications.
Abstract In the adult brain, self-renewing radial-glia like (RGL) progenitor cells have been shown to reside in the subventricular zone and the subgranular zone of the hippocampus. A large body of evidence shows that experiences such as learning, enriched environment and stress can alter proliferation and differentiation of RGL progenitor cells. The progenitor cells present in the subgranular zone of the hippocampus divide to give rise to newborn neurons that migrate to the dentate gyrus where they differentiate into adult granule neurons. These newborn neurons have been found to have a unique role in certain type...
Source: Experimental Neurology - June 3, 2020 Category: Neurology Authors: Redell JB, Maynard ME, Underwood EL, Vita SM, Dash PK, Kobori N Tags: Exp Neurol Source Type: research

Regulation of JNK signaling pathway and RIPK3/AIF in necroptosis-mediated global cerebral ischemia/reperfusion injury in rats.
Abstract Receptor-interacting protein kinase 3 (RIPK3) 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 (I/R) injury. The purpose of this study was to investigate the effects of interactions between the RIPK3 and apoptosis-inducing factor (AIF) 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 (rAAV) and JNK-specific inhibit...
Source: Experimental Neurology - June 2, 2020 Category: Neurology Authors: Hu W, Wu X, Yu D, Zhao L, Zhu X, Li X, Huang T, Chu Z, Xu Y Tags: Exp Neurol Source Type: research

Increased epileptogenicity in a mouse model of neurofibromatosis type 1.
CONCLUSIONS: 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 Nf1+/- mouse model in future mechanistic studies. PMID: 32502580 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 2, 2020 Category: Neurology Authors: Sabetghadam A, Wu C, Liu J, Zhang L, Reid AY Tags: Exp Neurol Source Type: research

Plasticity of thoracic interneurones rostral to a lateral spinal cord lesion.
Abstract 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 18 weeks 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 dend...
Source: Experimental Neurology - May 25, 2020 Category: Neurology Authors: Meehan CF, Ford TW, Kirkwood PA Tags: Exp Neurol Source Type: research

Lentivirally administered glial cell line-derived neurotrophic factor promotes post-ischemic neurological recovery, brain remodeling and contralesional pyramidal tract plasticity by regulating axonal growth inhibitors and guidance proteins.
Abstract Owing to its potent longterm neuroprotective and neurorestorative properties, glial cell line-derived neurotrophic factor (GDNF) 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...
Source: Experimental Neurology - May 23, 2020 Category: Neurology Authors: Beker M, Caglayan AB, Beker MC, Altunay S, Karacay R, Dalay A, Altıntas MO, Kose GT, Hermann DM, Kilic E Tags: Exp Neurol Source Type: research

The CCL2/CCR2 axis is critical to recruiting macrophages into acellular nerve allograft bridging a nerve gap to promote angiogenesis and regeneration.
Abstract Acellular nerve allografts (ANAs) 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 por...
Source: Experimental Neurology - May 22, 2020 Category: Neurology Authors: Pan D, Acevedo-Cintron JA, Sayanagi J, Snyder-Warwick AK, Mackinnon SE, Wood MD Tags: Exp Neurol Source Type: research

ENT1 inhibition attenuates apoptosis by activation of cAMP/pCREB/Bcl2 pathway after MCAO in rats.
CONCLUSIONS: 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. PMID: 32445645 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 20, 2020 Category: Neurology Authors: Zhang D, Jin W, Liu H, Liang T, Peng Y, Zhang J, Zhang Y Tags: Exp Neurol Source Type: research

A new model of repeat mTBI in adolescent rats.
Abstract Sports-related injury is frequently associated with repeated diffuse and mild traumatic brain injury (mTBI). We combined two existing models for inducing TBI in rats, the Impact Acceleration and Controlled Cortical Impact models, to create a new method relevant to the study of cognitive sequelae of repeat mTBI in adolescent athletes. Repeated mTBI, such as those incurred in sports, can result in a wide range of outcomes, with many individuals experiencing no chronic sequela while others develop profound cognitive and behavioral impairments, typically in the absence of lasting motor symptoms or gross tissu...
Source: Experimental Neurology - May 19, 2020 Category: Neurology Authors: Ondek K, Brevnova O, Jimenez-Ornelas C, Vergara A, Zwienenberg M, Gurkoff G Tags: Exp Neurol Source Type: research

Delayed recanalization after MCAO ameliorates ischemic stroke by inhibiting apoptosis via HGF/c-met/STAT3/Bcl-2 pathway in rats.
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. PMID: 32428505 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 16, 2020 Category: Neurology Authors: Tang H, Gamdzyk M, Huang L, Gao L, Lenahan C, Kang R, Tang J, Xia Y, Zhang JH Tags: Exp Neurol Source Type: research

Regeneration of adult rat sensory and motor neuron axons through chimeric peroneal nerve grafts containing donor Schwann cells engineered to express different neurotrophic factors.
Abstract Large peripheral nerve (PN) 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 ex vivo with Schwann cells (SCs) transduced with lentiviral vectors (LV) to express different growth factors (BDNF, CNTF or NT-3) supported the regeneration of axons across a 1 cm peroneal nerve defect (Godinho et al., 2013). Graft morphology, the number of regrown axons, the ratio of myelinated to unmyelinated axons, and hindlimb locomotor function differed depending on the growth factor engineered in...
Source: Experimental Neurology - May 15, 2020 Category: Neurology Authors: Godinho MJ, Staal JL, Krishnan VS, Hodgetts SI, Pollett MA, Goodman DP, Teh L, Verhaagen J, Plant GW, Harvey AR Tags: Exp Neurol Source Type: research

Postnatal exposure to low doses of Chlorpyrifos induces long-term effects on 5C-SRTT learning and performance, cholinergic and GABAergic systems and BDNF expression.
ez-Santed F Abstract 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 (CPF) is the most widely used organophosphate compound 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 the least studied. Despite the abundant empirical work made in the last decades on developmental CPF exposure, th...
Source: Experimental Neurology - May 6, 2020 Category: Neurology Authors: Perez-Fernandez C, Morales-Navas M, Guardia-Escote L, Colomina MT, Giménez E, Sánchez-Santed F Tags: Exp Neurol Source Type: research

Differential effects of SNARE-dependent gliotransmission on behavioral phenotypes in a mouse model of Huntington's disease.
Abstract Huntington's disease (HD) 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 (mHTT) in astrocytes to HD pathogenesis. Astrocytes exhibit SNARE-dependent exocytosis and gliotransmission, which can be hampered by transgenic expression of dominant negative SNARE (dnSNARE) 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 ...
Source: Experimental Neurology - May 6, 2020 Category: Neurology Authors: King AC, Wood TE, Rodriquez E, Parpura V, Gray M Tags: Exp Neurol Source Type: research

Striatal Nurr1, but not FosB expression links a levodopa-induced dyskinesia phenotype to genotype in fisher 344 vs. Lewis hemiparkinsonian rats.
Abstract Numerous genes, and alterations in their expression, have been identified as risk factors for developing levodopa-induced dyskinesia (LID). However, our understanding of the complexities of molecular changes remains insufficient for development of clinical treatment. In the current study we used gene array, in situ hybridization, immunohistochemistry, and microdialysis to provide a unique compare and contrast assessment of the relationship of four candidate genes to LID, employing three genetically distinct rat strains (Sprague-Dawley (SD), Fischer-344 (F344) and Lewis-RT.1) showing differences in dyskine...
Source: Experimental Neurology - May 5, 2020 Category: Neurology Authors: Steece-Collier K, Collier TJ, Lipton JW, Stancati JA, Winn ME, Cole-Strauss A, Sellnow R, Conti MM, Mercado NM, Nillni EA, Sortwell CE, Manfredsson FP, Bishop C Tags: Exp Neurol Source Type: research

Resveratrol reduces cerebral edema through inhibition of de novo SUR1 expression induced after focal ischemia.
Aguilera P Abstract Cerebral edema is a clinical problem that frequently follows ischemic infarcts. Sulfonylurea receptor 1 (SUR1) is an inducible protein that can form a heteromultimeric complex with aquaporin 4 (AQP4) that mediate the ion/water transport involved in brain tissue swelling. Transcription of the Abcc8 gene coding for SUR1 depends on the activity of transcriptional factor SP1, which is modulated by the cellular redox environment. Since oxidative stress is implicated in the induced neuronal damage in ischemia and edema formation, the present study aimed to evaluate if the antioxidant resveratrol (RS...
Source: Experimental Neurology - May 4, 2020 Category: Neurology Authors: Alquisiras-Burgos I, Ortiz-Plata A, Franco-Pérez J, Millán A, Aguilera P Tags: Exp Neurol Source Type: research

Long-term beneficial effects of hematopoietic growth factors on brain repair in the chronic phase of severe traumatic brain injury.
Abstract Severe traumatic brain injury (TBI) 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 severe TBI model in young adult mice, this study examined the restorative efficacy of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF), on brain repair in the chronic phase of TBI. SCF and G-CSF alone or combination (SCF + G-CSF) treatment were administered at 3...
Source: Experimental Neurology - April 29, 2020 Category: Neurology Authors: Qiu X, Ping S, Kyle M, Chin L, Zhao LR Tags: Exp Neurol Source Type: research

A novel approach to treatment of thromboembolic stroke in mice: Redirecting neutrophils toward a peripherally implanted CXCL1-soaked sponge.
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. PMID: 32360283 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 29, 2020 Category: Neurology Authors: Stamatovic SM, Phillips CM, Keep RF, Andjelkovic AV Tags: Exp Neurol Source Type: research

Benchmarking pluripotent stem cell-derived organoid models.
Abstract Cerebral organoids are stem cell-derived, self-organizing three-dimensional cultures. Owing to the remarkable degree to which they recreate the cellular diversity observed in the human brain, they have attracted significant interest as a novel model system for research and drug development, as well as capturing the public imagination. However, many questions remain about the extent to which these cultures recapitulate neurodevelopment and the defining features of the human brain. To clarify the fidelity of human organoid models, Bhaduri and colleagues compared the molecular profile of brain organoid cells...
Source: Experimental Neurology - April 27, 2020 Category: Neurology Authors: Angeles AL, Tunbridge EM Tags: Exp Neurol Source Type: research

Mitochondria focused neurotherapeutics for spinal cord injury.
Abstract The mitochondrion is a double membrane structured organelle involved in a variety of regulatory functions such as calcium signaling, production of adenosine triphosphate, apoptosis, reactive oxygen species generation, cell growth, and cell cycling. Impaired mitochondrial function is evident in various neurological disorders stemming from both acute and chronic neural injury. Herein, we review the role of mitochondrial regulation in maintaining cellular homeostasis, the consequences of their dysfunction in relation to pathophysiology after neurotrauma, approaches being used to promote their bioenergetic in...
Source: Experimental Neurology - April 27, 2020 Category: Neurology Authors: Rabchevsky AG, Michael FM, Patel SP Tags: Exp Neurol Source Type: research

Learning to promote recovery after spinal cord injury.
Abstract The present review explores the concept of learning within the context of neurorehabilitation after spinal cord injury (SCI). The aim of physical therapy and neurorehabilitation is to bring about a lasting change in function-to encourage learning. Traditionally, it was assumed that the adult spinal cord is hardwired-immutable and incapable of learning. Research has shown that neurons within the lower (lumbosacral) 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 spina...
Source: Experimental Neurology - April 27, 2020 Category: Neurology Authors: Grau JW, Baine RE, Bean PA, Davis JA, Fauss GN, Henwood MK, Hudson KE, Johnston DT, Tarbet MM, Strain MM Tags: Exp Neurol Source Type: research

PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry.
Abstract Although approximately 90% of the U.S. population will experience a traumatic event within their lifetime, only a fraction of those traumatized individuals will develop posttraumatic stress disorder (PTSD). In fact, approximately 7 out of 100 people in the U.S. will be afflicted by this debilitating condition, which suggests there is substantial inter-individual variability in susceptibility to PTSD. This uncertainty regarding who is susceptible to PTSD necessitates a thorough understanding of the neurobiological processes that underlie PTSD development in order to build effective predictive models for th...
Source: Experimental Neurology - April 25, 2020 Category: Neurology Authors: Harnett NG, Goodman AM, Knight DC Tags: Exp Neurol Source Type: research

Mitochondria in Alzheimer's disease and their potential role in Alzheimer's proteostasis.
Abstract Alzheimer's disease (AD) is a progressive brain disorder characterized by memory loss and the accumulation of two insoluble protein aggregates, tau neurofibrillary tangles and beta-amyloid plaques. Widespread mitochondrial dysfunction also occurs and mitochondria from AD patients display changes in number, ultrastructure, and enzyme activities. Mitochondrial dysfunction in AD presumably links in some way to its other disease characteristics, either as a cause or consequence. This review characterizes AD-associated mitochondrial perturbations and considers their position in its pathologic hierarchy. It foc...
Source: Experimental Neurology - April 24, 2020 Category: Neurology Authors: Weidling IW, Swerdlow RH Tags: Exp Neurol Source Type: research

Chronic hyperammonemia causes a hypoglutamatergic and hyperGABAergic metabolic state associated with neurobehavioral abnormalities in zebrafish larvae.
a M Abstract 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 concen...
Source: Experimental Neurology - April 24, 2020 Category: Neurology Authors: Probst J, Kölker S, Okun JG, Kumar A, Gursky E, Posset R, Hoffmann GF, Peravali R, Zielonka M Tags: Exp Neurol Source Type: research

Progesterone treatment following traumatic brain injury in the 11-day-old rat attenuates cognitive deficits and neuronal hyperexcitability in adolescence.
Abstract Traumatic brain injury (TBI) in children younger than 4 years old results in cognitive and psychosocial deficits in adolescence and adulthood. At 4 weeks following closed head injury on postnatal day 11, male and female rats exhibited impairment in novel object recognition memory (NOR) along with an increase in open arm time in the elevated plus maze (EPM), suggestive of risk-taking behaviors. This was accompanied by an increase in intrinsic excitability and frequency of spontaneous excitatory post-synaptic currents (EPSCs), and a decrease in the frequency of spontaneous inhibitory post-synaptic curre...
Source: Experimental Neurology - April 23, 2020 Category: Neurology Authors: Lengel D, Huh JW, Barson JR, Raghupathi R Tags: Exp Neurol Source Type: research

A comparative assessment of lengthening followed by end-to-end repair and isograft repair of chronically injured peripheral nerves.
In this study, we compared the use of nerve lengthening/end-to-end repair (LETER) 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. Nonethele...
Source: Experimental Neurology - April 22, 2020 Category: Neurology Authors: Howarth HM, Orozco E, Lovering RM, Shah SB Tags: Exp Neurol Source Type: research

Increased PINK1/Parkin-mediated mitophagy explains the improved brain protective effects of slow rewarming following hypothermia after cardiac arrest in rats.
Abstract Cerebral ischemia-reperfusion (I/R) after cardiac arrest (CA) induces mitochondrial dysfunction, and the timely removal of damaged mitochondria by mitophagy is reported to protect against cerebral I/R injury. Therapeutic hypothermia (TH) 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 di...
Source: Experimental Neurology - April 21, 2020 Category: Neurology Authors: Hu Y, Sun D, Li Y, Wang X, Jiang W, Shi H, Cui D Tags: Exp Neurol Source Type: research

Protective effects of phenelzine administration on synaptic and non-synaptic cortical mitochondrial function and lipid peroxidation-mediated oxidative damage following TBI in young adult male rats.
Abstract Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction of lipid peroxidation (LP). 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 phenelz...
Source: Experimental Neurology - April 20, 2020 Category: Neurology Authors: Hill RL, Singh IN, Wang JA, Kulbe JR, Hall ED Tags: Exp Neurol Source Type: research

Moderate exercise has beneficial effects on mouse ischemic stroke by enhancing the functions of circulating endothelial progenitor cell-derived exosomes.
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. PMID: 32325158 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 20, 2020 Category: Neurology Authors: Wang J, Liu H, Chen S, Zhang W, Chen Y, Yang Y Tags: Exp Neurol Source Type: research

Neuroregenerative and protective functions of Leukemia Inhibitory Factor in perinatal hypoxic-ischemic brain injury.
Abstract 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 24 h after birth. Here we show that Leukemia Inhibitory Factor (LIF) functions as an essential injury-induced neurotrophic cytokine in the CNS and that non-invasively administering LIF as late as 3 days after a hypoxic-ischemic insult improves neurological function. Using a mouse model of late preterm...
Source: Experimental Neurology - April 19, 2020 Category: Neurology Authors: Lin J, Niimi Y, Clausi MG, Kanal HD, Levison SW Tags: Exp Neurol Source Type: research

Neurovascular protection by peroxisome proliferator-activated receptor α in ischemic stroke.
Neurovascular protection by peroxisome proliferator-activated receptor α in ischemic stroke. Exp Neurol. 2020 Apr 19;:113323 Authors: Boese AC, Lee JP, Hamblin MH Abstract Ischemic stroke is a leading cause of death and disability worldwide. Currently, the only pharmacological therapy for ischemic stroke is thrombolysis with tissue plasminogen activator that has a narrow therapeutic window and increases the risk of intracerebral hemorrhage. New pharmacological treatments for ischemic stroke are desperately needed, but no neuroprotective drugs have successfully made it through clinical trials. Be...
Source: Experimental Neurology - April 19, 2020 Category: Neurology Authors: Boese AC, Lee JP, Hamblin MH Tags: Exp Neurol Source Type: research

Haploinsufficiency of X-linked intellectual disability gene CASK induces post-transcriptional changes in synaptic and cellular metabolic pathways.
Abstract Heterozygous mutations in the X-linked gene CASK are associated with intellectual disability, microcephaly, pontocerebellar hypoplasia, optic nerve hypoplasia and partially penetrant seizures in girls. The Cask+/- heterozygous knockout female mouse phenocopies the human disorder and exhibits postnatal microencephaly, cerebellar hypoplasia and optic nerve hypoplasia. It is not known if Cask+/- mice also display seizures, nor is known the molecular mechanism by which CASK haploinsufficiency produces the numerous documented phenotypes. 24-h video electroencephalography demonstrates that despite sporadic seiz...
Source: Experimental Neurology - April 16, 2020 Category: Neurology Authors: Patel PA, Liang C, Arora A, Vijayan S, Ahuja S, Wagley PK, Settlage R, Lew L, Goodkin HP, Lazar I, Srivastava S, Mukherjee K Tags: Exp Neurol Source Type: research

Early life stress increases vulnerability to the sequelae of pediatric mild traumatic brain injury.
JJ, Bondi CO, Kline AE Abstract Early life stress (ELS) 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 (mTBI) on cognition, hippocampal inflammation, and plasticity. Male rats were subjected to maternal separation for 180 min per day (MS180) or used as controls (CONT) during the first 21 post-natal (P...
Source: Experimental Neurology - April 16, 2020 Category: Neurology Authors: Diaz-Chávez A, Lajud N, Roque A, Cheng JP, Meléndez-Herrera E, Valdéz-Alarcón JJ, Bondi CO, Kline AE Tags: Exp Neurol Source Type: research

Heparin ameliorates cerebral edema and improves outcomes following status epilepticus by protecting endothelial glycocalyx in mice.
Abstract Blood brain barrier (BBB) hyperpermeability and brain edema contribute to increased seizure susceptibility and brain injury in status epilepticus (SE). 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...
Source: Experimental Neurology - April 16, 2020 Category: Neurology Authors: Li X, Zhu J, Liu K, Hu Y, Huang K, Pan S Tags: Exp Neurol Source Type: research

Evaluation of cell transplant-mediated attenuation of diffuse injury in experimental autoimmune encephalomyelitis using onVDMP CEST MRI.
Abstract 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 (EAE) mouse model of multiple sclerosis (MS), we studied attenuation of the diffuse injury characteristic of EAE and MS by transplanted glial-restricted precursor cells (GRPs). We assessed the potential of on-resonance variable delay multiple pulse (onVDMP) chemical exchange saturation transfer (CEST) MRI to visualize this attenuation. Allogeneic GRPs transplanted in the motor cortex or lateral ventricles atten...
Source: Experimental Neurology - April 15, 2020 Category: Neurology Authors: Thomas AM, Li S, Chu C, Shats I, Xu J, Calabresi PA, van Zijl PCM, Walczak P, Bulte JWM Tags: Exp Neurol Source Type: research