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

Differential glucose and beta-hydroxybutyrate metabolism confers an intrinsic neuroprotection to the immature brain in a rat model of neonatal hypoxia ischemia.
Abstract Neonatal hypoxia ischemia (HI) 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 (HI performed at postnatal days 3, 7 and 11,...
Source: Experimental Neurology - April 15, 2020 Category: Neurology Authors: Odorcyk FK, Duran-Carabali LE, Rocha DS, Sanches EF, Martini AP, Venturin GT, Greggio S, da Costa JC, Kucharski LC, Zimmer ER, Netto CA Tags: Exp Neurol Source Type: research

Axonal transport dysfunction of mitochondria in traumatic brain injury: A novel therapeutic target.
PMID: 32302676 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 14, 2020 Category: Neurology Authors: Shin SS, Karlsson M, Mazandi VM, Ranganathan A, Howell T, Delso N, Kilbaugh TJ Tags: Exp Neurol Source Type: research

Quantitative susceptibility mapping depicts severe myelin deficit and iron deposition in a transgenic model of multiple system atrophy.
r J Abstract Despite internationally established diagnostic criteria, multiple system atrophy (MSA) 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 post-mortem. Here, we examine whether myelin deficit observed in a transgenic murine model of MSA can be visualized and quantified in vivo using specific magnetic resonance imaging (MRI) approaches. Reduced myelin content was measured histologically in prototypical white matter as well as mixed grey...
Source: Experimental Neurology - April 14, 2020 Category: Neurology Authors: Lambrecht V, Hanspach J, Hoffmann A, Seyler L, Mennecke A, Straub S, Marxreiter F, Bäuerle T, Laun FB, Winkler J Tags: Exp Neurol Source Type: research

Calpain mediated expansion of CD4+ cytotoxic T cells in rodent models of Parkinson's disease.
Abstract Parkinson's disease (PD), a debilitating progressive degenerative movement disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra (SN), 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 ...
Source: Experimental Neurology - April 14, 2020 Category: Neurology Authors: Haque A, Samantaray S, Knaryan VH, Capone M, Hossain A, Matzelle D, Chandran R, Shields DC, Farrand AQ, Boger HA, Banik NL Tags: Exp Neurol Source Type: research

Effect of fluoxetine on HIF-1 α- Netrin/VEGF cascade, angiogenesis and neuroprotection in a rat model of transient middle cerebral artery occlusion.
Effect of fluoxetine on HIF-1α- Netrin/VEGF cascade, angiogenesis and neuroprotection in a rat model of transient middle cerebral artery occlusion. Exp Neurol. 2020 Apr 12;:113312 Authors: Hu Q, Liu L, Zhou L, Lu H, Wang J, Chen X, Wang Q Abstract 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-1α-Netrin/VEGF cascade, angiogenesis and neuroprotection using a rat model of transient middle cerebral artery occlusion (tMCAO). The rats were given fluoxetin...
Source: Experimental Neurology - April 12, 2020 Category: Neurology Authors: Hu Q, Liu L, Zhou L, Lu H, Wang J, Chen X, Wang Q Tags: Exp Neurol Source Type: research

Neuroprotective and neuro-rehabilitative effects of acute purinergic receptor P2X4 (P2X4R) blockade after ischemic stroke.
Abstract 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 (ATP), regulates activation of myeloid immune cells (infiltrating monocytes/macrophages and brain-resident microglia) 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 bot...
Source: Experimental Neurology - April 11, 2020 Category: Neurology Authors: Srivastava P, Cronin CG, Scranton VL, Jacobson KA, Liang BT, Verma R Tags: Exp Neurol Source Type: research

Mitochondrial biogenesis as a therapeutic target for traumatic and neurodegenerative CNS diseases.
Abstract Central nervous system (CNS) diseases, both traumatic and neurodegenerative, are characterized by impaired mitochondrial bioenergetics and often disturbed mitochondrial dynamics. The dysregulation observed in these pathologies leads to defective respiratory chain function and reduced ATP production, thereby promoting neuronal death. As such, attenuation of mitochondrial dysfunction through induction of mitochondrial biogenesis (MB) is a promising, though still underexplored, therapeutic strategy. MB is a multifaceted process involving the integration of highly regulated transcriptional events, lipid membr...
Source: Experimental Neurology - April 11, 2020 Category: Neurology Authors: Simmons EC, Scholpa NE, Schnellmann RG Tags: Exp Neurol Source Type: research

Microglia and macrophage metabolism in CNS injury and disease: The role of immunometabolism in neurodegeneration and neurotrauma.
Abstract Innate immune responses, particularly activation of macrophages and microglia, are increasingly implicated in CNS disorders. It is now appreciated that the heterogeneity of functions adopted by these cells dictates neuropathophysiology. Research efforts to characterize the range of pro-inflammatory and anti-inflammatory phenotypes and functions adopted by microglia and macrophages are fueled by the potential for inflammatory cells to both exacerbate neurodegeneration and promote repair/disease resolution. The stimulation-based, M1/M2 classification system has emerged over the last decade as a common langu...
Source: Experimental Neurology - April 11, 2020 Category: Neurology Authors: Devanney NA, Stewart AN, Gensel JC Tags: Exp Neurol Source Type: research

Mitochondrial damage & lipid signaling in traumatic brain injury.
Mitochondrial damage & lipid signaling in traumatic brain injury. Exp Neurol. 2020 Apr 11;:113307 Authors: Lamade AM, Anthonymuthu TS, Hier ZE, Gao Y, Kagan VE, Bayır H Abstract Mitochondria are essential for neuronal function because they serve not only to sustain energy and redox homeostasis but also are harbingers of death. A dysregulated mitochondrial network can cascade until function is irreparably lost, dooming cells. TBI is most prevalent in the young and comes at significant personal and societal costs. Traumatic brain injury (TBI) triggers a biphasic and mechanistically heterogenous res...
Source: Experimental Neurology - April 11, 2020 Category: Neurology Authors: Lamade AM, Anthonymuthu TS, Hier ZE, Gao Y, Kagan VE, Bayır H Tags: Exp Neurol Source Type: research

Dissociated roles of dorsal and ventral hippocampus in recall and extinction of conditioned fear in male and female juvenile rats.
Abstract 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 (P) 18 female, but not in male, rats. Given the hippocampus (HPC) is critical for context-specific extinction in adult rodents, we investigated dorsal or ventral hippocampus (dHPC or vHPC) involvement in context-specific ex...
Source: Experimental Neurology - April 10, 2020 Category: Neurology Authors: Park CHJ, Ganella DE, Perry CJ, Kim JH Tags: Exp Neurol Source Type: research

Functional imaging of the piriform cortex in focal epilepsy.
Abstract Experiments in animal models have identified specific brain regions such as the deep anterior piriform cortex as important for controlling the initiation or propagation of both generalized and focal seizure activity. However, there is little experimental evidence to translate these observations to the control of focal seizures in humans. Here, we summarize findings from different hemodynamic and neurotransmitter functional imaging studies in groups of patients with focal epilepsies arising from different cortical locations in support of a common area of brain dysfunction in focal epilepsies. PMID: 32...
Source: Experimental Neurology - April 9, 2020 Category: Neurology Authors: Koepp M, Galovic M Tags: Exp Neurol Source Type: research

Assessment of direct knowledge of the human olfactory system.
PMID: 32278646 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 9, 2020 Category: Neurology Authors: Lane G, Zhou G, Noto T, Zelano C Tags: Exp Neurol Source Type: research

Presynaptic Caytaxin prevents apoptosis via deactivating DAPK1 in the acute phase of cerebral ischemic stroke.
Abstract Death-associated protein kinase 1 (DAPK1) 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 (BNIP-2), increases and interacts with DAPK1 as early as 2 h after middle cerebral artery occlusion (MCAO) in the penumbra area of mouse brain. Furthermore, Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity. Silencing...
Source: Experimental Neurology - April 8, 2020 Category: Neurology Authors: Wang S, Chen K, Yu J, Wang X, Li Q, Lv F, Shen H, Pei L Tags: Exp Neurol Source Type: research

Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3 β.
Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3β. Exp Neurol. 2020 Apr 07;:113302 Authors: Liu H, Wu X, Luo J, Zhao L, Li X, Guo H, Bai H, Cui W, Guo W, Feng D, Qu Y Abstract The effects of current treatment strategies for ischemic stroke are weakened by ischemia-reperfusion (I/R) injury. Effective treatments targeting I/R injury are still insufficient. Adiponectin (APN), a fat-derived hormone, has a wide range of antioxidative and anti-inflammatory effects. However, the application of APN to the...
Source: Experimental Neurology - April 7, 2020 Category: Neurology Authors: Liu H, Wu X, Luo J, Zhao L, Li X, Guo H, Bai H, Cui W, Guo W, Feng D, Qu Y Tags: Exp Neurol Source Type: research

Response of hypogastric afferent fibers to bladder distention or irritation in cats.
Abstract The goal of this study in anesthetized cats was to identify silent hypogastric nerve (HGN) 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 (AA) 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 wer...
Source: Experimental Neurology - April 3, 2020 Category: Neurology Authors: Guo W, Shapiro K, Wang Z, Pace N, Cai H, Shen B, Wang J, de Groat WC, Tai C, Beckel JM Tags: Exp Neurol Source Type: research

Alternative substrate metabolism depends on cerebral metabolic state following traumatic brain injury.
Abstract Decreases in energy metabolism following traumatic brain injury (TBI) 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 co...
Source: Experimental Neurology - April 2, 2020 Category: Neurology Authors: Greco T, Vespa PM, Prins ML Tags: Exp Neurol Source Type: research

Low-pressure fluid percussion minimally adds to the sham craniectomy-induced neurobehavioral changes: Implication for experimental traumatic brain injury model.
Abstract Modeling experimental traumatic brain injury (TBI) 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 (FPI) is the most extensively used model to represent clinical phenotypes. Nevertheless, the surgical 'sham' procedure (craniectomy), 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 neurobehavior...
Source: Experimental Neurology - March 30, 2020 Category: Neurology Authors: Aleem M, Goswami N, Kumar M, Manda K Tags: Exp Neurol Source Type: research

Molecular profile of the rat peri-infarct region four days after stroke: Study with MANF.
In this study, we examine the molecular profile of the peri-infarct region on post-stroke day four, time when reparative processes are ongoing. We used a multiomics approach, involving RNA sequencing, and mass spectrometry-based proteomics and metabolomics to characterize molecular changes in the peri-infarct region. We also took advantage of our previously developed method to express transgenes in the peri-infarct region where self-complementary adeno-associated virus (AAV) vectors were injected into the brain parenchyma on post-stroke day 2. We have previously used this method to show that mesencephalic astrocyte-derived...
Source: Experimental Neurology - March 27, 2020 Category: Neurology Authors: Teppo J, Vaikkinen A, Stratoulias V, Mätlik K, Anttila JE, Smolander OP, Pöhö P, Harvey BK, Kostiainen R, Airavaara M Tags: Exp Neurol Source Type: research

Safinamide's potential in treating nondystrophic myotonias: Inhibition of skeletal muscle voltage-gated sodium channels and skeletal muscle hyperexcitability in vitro and in vivo.
In conclusion, safinamide is a potent voltage and frequency dependent blocker of skeletal muscle sodium channels. Accordingly, the drug was able to counteract abnormal muscle hyperexcitability induced by 9-AC, both in vitro and in vivo. Thus, this study suggests that safinamide may have potential in treating myotonia and warrants further preclinical and human studies to fully evaluate this possibility. PMID: 32205118 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 20, 2020 Category: Neurology Authors: Desaphy JF, Farinato A, Altamura C, De Bellis M, Imbrici P, Tarantino N, Caccia C, Melloni E, Padoani G, Vailati S, Keywood C, Carratù MR, De Luca A, Conte D, Pierno S Tags: Exp Neurol Source Type: research

Olesoxime improves cerebral mitochondrial dysfunction and enhances A β levels in preclinical models of Alzheimer's disease.
CONCLUSIONS: TRO19622 improves mitochondrial dysfunction but enhances Aβ levels in disease models of AD. Further studies must evaluate whether TRO19622 offers benefits at the mitochondrial level despite the increased formation of Aβ, which could be harmful. PMID: 32199815 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 18, 2020 Category: Neurology Authors: Eckert GP, Eckert SH, Eckmann J, Hagl S, Muller WE, Friedland K Tags: Exp Neurol Source Type: research

Optogenetic control of perforant pathway kindled seizures by photoinhibition of CA3 after insertion of Jaws into CA3 neuronal cells.
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 Jaws in neurons was injected into CA1 of the kindled rats. One week later, the kindled rats were stimulated at afterdischarge (AD) threshold under red light illumination to CA3; and duration of AD (ADD), generalized seizur...
Source: Experimental Neurology - March 9, 2020 Category: Neurology Authors: Farzaneh M, Sayyah M, Mirzapourdelavar H, Pourbadie HG, Zibaii MI, Latifi H Tags: Exp Neurol Source Type: research