Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.
Abstract Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the s...
Source: Experimental Neurology - July 19, 2017 Category: Neurology Authors: Taha O, Opitz T, Mueller M, Pitsch J, Becker A, Evert BO, Beck H, Jeub M Tags: Exp Neurol Source Type: research

Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib.
Abstract Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn...
Source: Experimental Neurology - July 18, 2017 Category: Neurology Authors: Wei JY, Liu CC, Ouyang HD, Ma C, Xie MX, Liu M, Lei WL, Ding HH, Wu SL, Xin WJ Tags: Exp Neurol Source Type: research

Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model.
In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We...
Source: Experimental Neurology - July 17, 2017 Category: Neurology Authors: Lee H, Jung S, Lee P, Jeong Y Tags: Exp Neurol Source Type: research

EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.
Abstract Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transdu...
Source: Experimental Neurology - July 14, 2017 Category: Neurology Authors: Kanemitsu M, Tsupykov O, Potter G, Boitard M, Salmon P, Zgraggen E, Gascon E, Skibo G, Dayer AG, Kiss JZ Tags: Exp Neurol Source Type: research

Optic nerve regeneration in mammals: Regenerated or spared axons?
Abstract Intraorbital optic nerve crush in rodents is widely used as a model to study axon regeneration in the adult mammalian central nervous system. Recent studies using appropriate genetic manipulations have revealed remarkable abilities of mature retinal ganglion cell (RGC) axons to regenerate after optic nerve injury, with some studies demonstrating that axons can then go on to re-innervate a number of central visual targets with partial functional restoration. However, one confounding factor inherent to optic nerve crush injury is the potential incompleteness of the initial lesion, leaving spared axons that ...
Source: Experimental Neurology - July 14, 2017 Category: Neurology Authors: Fischer D, Harvey AR, Pernet V, Lemmon VP, Park KK Tags: Exp Neurol Source Type: research

Sodium selenate activated Wnt/ β-catenin signaling and repressed amyloid-β formation in a triple transgenic mouse model of Alzheimer's disease.
Sodium selenate activated Wnt/β-catenin signaling and repressed amyloid-β formation in a triple transgenic mouse model of Alzheimer's disease. Exp Neurol. 2017 Jul 12;: Authors: Jin N, Zhu H, Liang X, Huang W, Xie Q, Xiao P, Ni J, Liu Q Abstract Accumulating evidences show that selenium dietary intake is inversely associated with the mortality of Alzheimer's disease (AD). Sodium selenate has been reported to reduce neurofibrillary tangles (NFT) in the tauopathic mouse models, but its effects on the Wnt/β-catenin signaling pathway and APP processing remain unknown during AD formation. In...
Source: Experimental Neurology - July 12, 2017 Category: Neurology Authors: Jin N, Zhu H, Liang X, Huang W, Xie Q, Xiao P, Ni J, Liu Q Tags: Exp Neurol Source Type: research

Critical role of EphA4 in early brain injury after subarachnoid hemorrhage in rat.
Abstract Early brain injury (EBI) is reported as a primary cause of mortality in subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been associated with blood-brain barrier integrity and pro-apoptosis. We aimed to investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male adult Sprague-Dawley rats were randomly divided into sham versus endovascular perforation model of SAH groups. SAH grade, neurological score, Evans blue dye extravasation, brain water content, mortality, Fluoro-Jade staining, immunofluorescence staining, and western blot experiments were performed after SAH. ...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Fan R, Enkhjargal B, Camara R, Yan F, Gong L, ShengtaoYao, Tang J, Chen Y, Zhang JH Tags: Exp Neurol Source Type: research

Myelination of axons emerging from neural progenitor grafts after spinal cord injury.
Abstract Neural progenitor cells (NPCs) grafted to sites of spinal cord injury (SCI) extend numerous axons over long distances and form new synaptic connections with host neurons. In the present study we examined the myelination of axons emerging from NPC grafts. Rat E14 multipotent NPCs constitutively expressing GFP were grafted into adult C5 spinal cord hemisection lesions; 3months later we examined graft-derived axonal diameter and myelination using transmission electron microscopy. 104 graft-derived axons were characterized. Axon diameter ranged from 0.15 to 1.70μm, and 24% of graft-derived axons were myeli...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Hunt M, Lu P, Tuszynski MH Tags: Exp Neurol Source Type: research

Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury.
Abstract Antipsychotic drugs, such as haloperidol (HAL), are prescribed in the clinic to manage traumatic brain injury (TBI)-induced agitation. While preclinical studies have consistently shown that once-daily administration of HAL hinders functional recovery after TBI in male rats, its effects in females are unknown. Hence, the objective of this study was to directly compare neurobehavioral and histological outcomes in both sexes to determine whether the reported deleterious effects of HAL extend to females. Anesthetized adult female and male rats received either a controlled cortical impact (CCI) or sham injury ...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Free KE, Greene AM, Bondi CO, Lajud N, de la Tremblaye PB, Kline AE Tags: Exp Neurol Source Type: research

Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders.
Abstract Immune molecules such as cytokines and chemokines and the cells that produce them within the brain, notably microglia, are critical for normal brain development. This recognition has in recent years led to the working hypothesis that inflammatory events during pregnancy, e.g. in response to infection, may disrupt the normal expression of immune molecules during critical stages of neural development and thereby contribute to the risk for neurodevelopmental disorders such as autism spectrum disorder (ASD). This hypothesis has in large part been shepherded by the work of Dr. Paul Patterson and colleagues, wh...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Bilbo SD, Block CL, Bolton JL, Hanamsagar R, Tran PK Tags: Exp Neurol Source Type: research

Age-related accumulation of phosphorylated mitofusin 2 protein in retinal ganglion cells correlates with glaucoma progression.
We examined the correlation between bioenergetics and axonal transport with mitochondrial mutation frequency and post-translational modifications of mitofusin 2 (Mfn2) in RGCs during glaucoma progression. No increase in the frequency of mtDNA mutations was detected, but we observed significant shifts in mitochondrial protein species. Mfn2 is a fusion protein that functions in mitochondrial biogenesis, maintenance, and mitochondrial transport. We demonstrate that Mfn2 accumulates selectively in RGCs during glaucomatous degeneration, that two novel states of Mfn2 exist in retina and ON, and identify a phosphorylated form tha...
Source: Experimental Neurology - July 3, 2017 Category: Neurology Authors: Nivison MP, Ericson NG, Green VM, Bielas JH, Campbell JS, Horner PJ Tags: Exp Neurol Source Type: research

Macrophage migration inhibitory factor: A multifaceted cytokine implicated in multiple neurological diseases.
Abstract Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated. Numerous studies have as...
Source: Experimental Neurology - July 2, 2017 Category: Neurology Authors: Leyton-Jaimes MF, Kahn J, Israelson A Tags: Exp Neurol Source Type: research

Evidence that activation of P2X7R does not exacerbate neuronal death after optic nerve transection and focal cerebral ischemia in mice.
Abstract Conflicting data in the literature about the function of P2X7R in survival following ischemia necessitates the conductance of in-depth studies. To investigate the impacts of activation vs inhibition of the receptor on neuronal survival as well as the downstream signaling cascades, in addition to optic nerve transection (ONT), 30min and 90min of middle cerebral artery occlusion (MCAo) models were performed in mice. Intracellular calcium levels were assessed in primary cortical neuron cultures. Here, we show that P2X7R antagonist Brilliant Blue G (BBG) decreased DNA fragmentation, infarct volume, brain swel...
Source: Experimental Neurology - June 29, 2017 Category: Neurology Authors: Caglayan B, Caglayan AB, Beker MC, Yalcin E, Beker M, Kelestemur T, Sertel E, Ozturk G, Kilic U, Sahin F, Kilic E Tags: Exp Neurol Source Type: research

Transient receptor potential melastatin 2 channels (TRPM2) mediate neonatal hypoxic-ischemic brain injury in mice.
We report that the infarct volumes were significantly smaller and behavioral outcomes were improved in both TRPM2(+/-) and TRPM2(-/-) mice compared to that of wildtype mice. Next, we found that TRPM2-null mice showed reduced dephosphorylation of GSK-3β following hypoxic ischemic injury unlike sham mice. TRPM2(+/-) and TRPM2(-/-) mice also had reduced activation of astrocytes and microglia in ipsilateral hemispheres, compared to wildtype mice. These findings suggest that TRPM2 channels play an essential role in mediating hypoxic-ischemic brain injury in neonatal mice. Genetically eliminating TRPM2 channels can provide ...
Source: Experimental Neurology - June 28, 2017 Category: Neurology Authors: Huang S, Turlova E, Li F, Bao MH, Szeto V, Wong R, Abussaud A, Wang H, Zhu S, Gao X, Mori Y, Feng ZP, Sun HS Tags: Exp Neurol Source Type: research

Sociability impairments in Genetic Absence Epilepsy Rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944.
Abstract Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neurological circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3.2 T-type calcium channel gene. Thus, the objective of this study ...
Source: Experimental Neurology - June 25, 2017 Category: Neurology Authors: Henbid MT, Marks WN, Collins MJ, Cain SM, Snutch TP, Howland JG Tags: Exp Neurol Source Type: research

Injury-induced gp130 cytokine signaling in peripheral ganglia is reduced in diabetes mellitus.
Abstract Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well-understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia. Mice were injected with either ...
Source: Experimental Neurology - June 20, 2017 Category: Neurology Authors: Niemi JP, Filous AR, DeFrancesco A, Lindborg JA, Malhotra NA, Wilson GN, Zhou B, Crish SD, Zigmond RE Tags: Exp Neurol Source Type: research

Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.
Abstract Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the ...
Source: Experimental Neurology - June 15, 2017 Category: Neurology Authors: Perez-Urrutia N, Mendoza C, Alvarez-Ricartes N, Oliveros-Matus P, Echeverria F, Grizzell JA, Barreto GE, Iarkov A, Echeverria V Tags: Exp Neurol Source Type: research

Low intensity rTMS has sex-dependent effects on the local response of glia following a penetrating cortical stab injury.
Abstract Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect o...
Source: Experimental Neurology - June 14, 2017 Category: Neurology Authors: Clarke D, Penrose MA, Harvey AR, Rodger J, Bates KA Tags: Exp Neurol Source Type: research

Clinical approaches to the development of a neuroprotective therapy for PD.
Abstract The development of a neuroprotective or disease-modifying therapy is the major unmet need in the management of Parkinson's Disease (PD) and the goal of much clinical and scientific research. However, despite enormous efforts and expense, no disease-modifying therapy for PD has been approved to date. Historically attempts to define such a therapy have been limited by confounding symptomatic/pharmacologic effects of the study intervention and the lack of a clear and well-defined regulatory and clinical development pathway that leads to a disease-modifying indication. Further, the costs of As a consequence, ...
Source: Experimental Neurology - June 13, 2017 Category: Neurology Authors: Olanow CW, Kieburtz K, Katz R Tags: Exp Neurol Source Type: research

Targeting urate to reduce oxidative stress in Parkinson disease.
Abstract Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and...
Source: Experimental Neurology - June 13, 2017 Category: Neurology Authors: Crotty GF, Ascherio A, Schwarzschild MA Tags: Exp Neurol Source Type: research

Overexpression of eIF4F components in meningiomas and suppression of meningioma cell growth by inhibiting translation initiation.
Abstract Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knock...
Source: Experimental Neurology - June 10, 2017 Category: Neurology Authors: Oblinger JL, Burns SS, Huang J, Pan L, Ren Y, Shen R, Douglas Kinghorn A, Bradley Welling D, Chang LS Tags: Exp Neurol Source Type: research

CNS disease diminishes the therapeutic functionality of bone marrow mesenchymal stem cells.
Abstract Mesenchymal stem cells (MSCs) have emerged as a potentially powerful cellular therapy for autoimmune diseases including multiple sclerosis (MS). Based on their success in treating animal models of MS like experimental autoimmune encephalomyelitis (EAE), MSCs have moved rapidly into clinical trials for MS. The majority of these trials use autologous MSCs derived from MS patients, although it remains unclear how CNS disease may affect these cells. Here, we report that bone marrow MSCs derived from EAE mice lack therapeutic efficacy compared to naïve MSCs in their ability to ameliorate EAE. Treatment wi...
Source: Experimental Neurology - June 9, 2017 Category: Neurology Authors: Sargent A, Bai L, Shano G, Karl M, Garrison E, Ranasinghe L, Planchon SM, Cohen J, Miller RH Tags: Exp Neurol Source Type: research

The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor- α represents a new antinociceptive signaling pathway in mice.
The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice. Exp Neurol. 2017 Jun 09;: Authors: Donvito G, Bagdas D, Toma W, Rahimpour E, Jackson A, Meade JA, AlSharari S, Kulkarni AR, Ivy Carroll F, Lichtman AH, Papke RL, Thakur GA, Imad Damaj M Abstract Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modul...
Source: Experimental Neurology - June 9, 2017 Category: Neurology Authors: Donvito G, Bagdas D, Toma W, Rahimpour E, Jackson A, Meade JA, AlSharari S, Kulkarni AR, Ivy Carroll F, Lichtman AH, Papke RL, Thakur GA, Imad Damaj M Tags: Exp Neurol Source Type: research

Fumarate decreases edema volume and improves functional outcome after experimental stroke.
CONCLUSIONS: A single intravenous bolus of MMF improved sensory-motor function after ischemic stroke, reduced edema formation, and increased the levels of the neuroprotective protein Hsp72 in the brain. The early increase in IL-10 and reduction in IL-12p70 in the brain combined with changes in systemic cytokine levels may also contribute to the functional recovery after pMCAO. PMID: 28602832 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 8, 2017 Category: Neurology Authors: Clausen BH, Lundberg L, Yli-Karjanmaa M, Martin NA, Svensson M, Alfsen MZ, Flæng SB, Lyngsø K, Boza-Serrano A, Nielsen HH, Hansen PB, Finsen B, Deierborg T, Illes Z, Lambertsen KL Tags: Exp Neurol Source Type: research

A novel IL-1RA-PEP fusion protein with enhanced brain penetration ameliorates cerebral ischemia-reperfusion injury by inhibition of oxidative stress and neuroinflammation.
In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP). Studies were carried out in transient middle cerebral artery occlusion (MCAO) in rats and oxygen glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons. In MCAO rat model, IL-1RA-PEP (50mg/kg) injected i.v., penetrated BBB effectively, and alleviated brain infarction, cerebral edema, neurological deficit score and motor performance as well as inhibited the inflammatory cytokines expression. Furthermore, our results firstly sh...
Source: Experimental Neurology - June 8, 2017 Category: Neurology Authors: Zhang DD, Zou MJ, Zhang YT, Fu WL, Xu T, Wang JX, Xia WR, Huang ZG, Gan XD, Zhu XM, Xu DG Tags: Exp Neurol Source Type: research

Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy.
Abstract Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about the status of this phenotype in epilepsy. Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in microglia-mediated synaptic pruning. Interestingly, in human and experimental epilepsy, altered mRNA levels of complement molecules were reported. Therefore, to identify a potential role for complement and microglia in the synaptodendritic pathology of epilepsy, we determined the prote...
Source: Experimental Neurology - June 7, 2017 Category: Neurology Authors: Wyatt SK, Witt T, Barbaro NM, Cohen-Gadol AA, Brewster AL Tags: Exp Neurol Source Type: research

Axonal dystrophy in the brain of mice with Sanfilippo syndrome.
Abstract Axonal dystrophy has been described as an early pathological feature of neurodegenerative disorders including Alzheimer's disease and amyotrophic lateral sclerosis. Axonal inclusions have also been reported to occur in several neurodegenerative lysosomal storage disorders including Mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome). This disorder results from a mutation in the gene encoding the lysosomal sulphatase sulphamidase, and as a consequence heparan sulphate accumulates, accompanied by secondarily-stored gangliosides. The precise basis of symptom generation in MPS IIIA has not been el...
Source: Experimental Neurology - June 7, 2017 Category: Neurology Authors: Beard H, Hassiotis S, Gai WP, Parkinson-Lawrence E, Hopwood JJ, Hemsley KM Tags: Exp Neurol Source Type: research

Rapid focal cooling attenuates cortical seizures in a primate epilepsy model.
Abstract Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in...
Source: Experimental Neurology - June 7, 2017 Category: Neurology Authors: Ren G, Yan J, Tao G, Gan Y, Li D, Yan X, Fu Y, Wang L, Wang W, Zhang Z, FengYue, Yang X Tags: Exp Neurol Source Type: research

Validation of an automated tractography method for the optic radiations as a biomarker of visual acuity in neurofibromatosis-associated optic pathway glioma.
Abstract INTRODUCTION: Fractional anisotropy (FA) of the optic radiations has been associated with vision deficit in multiple intrinsic brain pathologies including NF1 associated optic pathway glioma, but hand-drawn regions of interest used in previous tractography methods limit consistency of this potential biomarker. We created an automated method to identify white matter tracts in the optic radiations and compared this method to previously reported hand-drawn tractography. METHOD: Automated tractography of the optic radiation using probabilistic streamline fiber tracking between the lateral geniculate nucl...
Source: Experimental Neurology - June 3, 2017 Category: Neurology Authors: de Blank P, Fisher MJ, Gittleman H, Barnholtz-Sloan JS, Badve C, Berman JI Tags: Exp Neurol Source Type: research

Regulation of transient receptor potential cation channel subfamily V1 protein synthesis by the phosphoinositide 3-kinase/Akt pathway in colonic hypersensitivity.
Abstract The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor or vanilloid receptor 1 (VR1), is expressed in nociceptive neurons in the dorsal root ganglia (DRG) and participates in the transmission of pain. The present study investigated the underlying molecular mechanisms by which TRPV1 was regulated by nerve growth factor (NGF) signaling pathways in colonic hypersensitivity in response to colitis. We found that during colitis TRPV1 protein levels were significantly increased in specifically labeled colonic afferent neurons in both L1 and S1 DRGs. TRP...
Source: Experimental Neurology - June 3, 2017 Category: Neurology Authors: Shen S, Al-Thumairy HW, Hashmi F, Qiao LY Tags: Exp Neurol Source Type: research

Neuropathies in the setting of Neurofibromatosis tumor syndromes: Complexities and opportunities.
i S Abstract The term 'Neurofibromatosis' (NF) comprises a group of rare diseases with related clinical presentations but distinct genetic conditions. All currently known types - NF1, NF2 and Schwannomatosis - predispose afflicted individuals to the development of glial cell-derived (gliogenic) tumors. Furthermore, the occurrence of neuropathic symptoms, which add to the overall neurologic disability of patients, has been described in all disease entities. We show that neuropathic symptoms are a common and clinically important, yet infrequently studied feature in the NF spectrum. However, the clinical relevance an...
Source: Experimental Neurology - June 3, 2017 Category: Neurology Authors: Schulz A, Grafe P, Hagel C, Bäumer P, Morrison H, Mautner VF, Farschtschi S Tags: Exp Neurol Source Type: research

The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.
Abstract We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression mo...
Source: Experimental Neurology - June 3, 2017 Category: Neurology Authors: Geremia NM, Hryciw T, Bao F, Streijger F, Okon E, Lee JHT, Weaver LC, Dekaban GA, Kwon BK, Brown A Tags: Exp Neurol Source Type: research

Strength of cholinergic tone dictates the polarity of dopamine D2 receptor modulation of striatal cholinergic interneuron excitability in DYT1 dystonia.
Abstract Balance between cholinergic and dopaminergic signaling is central to striatal control of movement and cognition. In dystonia, a common disorder of movement, anticholinergic therapy is often beneficial. This observation suggests there is a pathological increase in cholinergic tone, yet direct confirmation is lacking. In DYT1, an early-onset genetic form of dystonia caused by a mutation in the protein torsinA (TorA), the suspected heightened cholinergic tone is commonly attributed to faulty dopamine D2 receptor (D2R) signaling where D2R agonists cause excitation of striatal cholinergic interneurons (ChIs), ...
Source: Experimental Neurology - June 3, 2017 Category: Neurology Authors: Scarduzio M, Zimmerman CN, Jaunarajs KL, Wang Q, Standaert DG, McMahon LL Tags: Exp Neurol Source Type: research

RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage.
In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection. SAH grade, neurological function, brain water content, Western blot, ROS assay, immunofluorescence and transmission electron microscopy were performed. SAH led to the upregulation of RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome. Nec-1 treatment reduced RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome, ...
Source: Experimental Neurology - June 2, 2017 Category: Neurology Authors: Zhou K, Shi L, Wang Z, Zhou J, Manaenko A, Reis C, Chen S, Zhang J Tags: Exp Neurol Source Type: research

A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.
This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity. PMID: 28579325 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 1, 2017 Category: Neurology Authors: Su P, Liu F Tags: Exp Neurol Source Type: research

Manipulating cognitive reserve: Pre-injury environmental conditions influence the severity of concussion symptomology, gene expression, and response to melatonin treatment in rats.
Abstract In an effort to understand the factors that contribute to heterogeneity in outcomes often associated with mTBI in youth, this study examined the role of premorbid differences in cognitive reserve on post-concussive symptoms (PCS), molecular markers, and treatment response. Male and female rats matured in one of three environmental conditions (Stress, Enrichment, Control), received a mTBI in adolescence, and were randomized to melatonin or placebo treatment. All animals underwent a behavioural test battery designed to examine PCS. Using prefrontal cortex and hippocampus tissue, expression of 9 genes was as...
Source: Experimental Neurology - June 1, 2017 Category: Neurology Authors: Yamakawa G, Salberg S, Barlow KM, Brooks BL, Esser M, Yeates KO, Mychasiuk R Tags: Exp Neurol Source Type: research

Developing a data sharing community for spinal cord injury research.
Abstract The rapid growth in data sharing presents new opportunities across the spectrum of biomedical research. Global efforts are underway to develop practical guidance for implementation of data sharing and open data resources. These include the recent recommendation of 'FAIR Data Principles', which assert that if data is to have broad scientific value, then digital representations of that data should be Findable, Accessible, Interoperable and Reusable (FAIR). The spinal cord injury (SCI) research field has a long history of collaborative initiatives that include sharing of preclinical research models and outco...
Source: Experimental Neurology - May 30, 2017 Category: Neurology Authors: Callahan A, Anderson KD, Beattie MS, Bixby JL, Ferguson AR, Fouad K, Jakeman LB, Nielson JL, Popovich PG, Schwab JM, Lemmon VP, FAIR Share Workshop Participants Tags: Exp Neurol Source Type: research

Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.
Abstract The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy ...
Source: Experimental Neurology - May 30, 2017 Category: Neurology Authors: Fazeli W, Zappettini S, Marguet SL, Grendel J, Esclapez M, Bernard C, Isbrandt D Tags: Exp Neurol Source Type: research

Nrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson's disease.
Abstract Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the cause of PD remains elusive, mitochondrial dysfunction and severe oxidative stress are strongly implicated in the cell death that characterizes the disease. Under oxidative stress, the master regulator of cellular redox status, nuclear factor erythroid 2 related factor 2 (Nrf2), is responsible for activating the transcription of several cytoprotective enzymes, namely glutathione peroxidase (GPx) and heme oxygenase-1 (HO-1). Nrf2 is a ...
Source: Experimental Neurology - May 25, 2017 Category: Neurology Authors: Moreira S, Fonseca I, Nunes MJ, Rosa A, Lemos L, Rodrigues E, Carvalho AN, Outeiro TF, Rodrigues CMP, Gama MJ, Castro-Caldas M Tags: Exp Neurol Source Type: research

Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.
Abstract Spinal cord injury (SCI) causes chronic pain in 65% of individuals. Unfortunately, current pain management is inadequate for many SCI patients. Rodent models could help identify how SCI pain develops, explore new treatment strategies, and reveal whether acute post-SCI morphine worsens chronic pain. However, few studies explore or compare SCI-elicited neuropathic pain in rats. Here, we sought to determine how different clinically relevant contusion SCIs in male and female rats affect neuropathic pain, and whether acute morphine worsens later chronic SCI pain. First, female rats received sham surgery, or 15...
Source: Experimental Neurology - May 25, 2017 Category: Neurology Authors: Gaudet AD, Ayala MT, Schleicher WE, Smith EJ, Bateman EM, Maier SF, Watkins LR Tags: Exp Neurol Source Type: research

Myeloid differentiation factor 88 is up-regulated in epileptic brain and contributes to experimental seizures in rats.
Abstract Accumulating evidence supports that activation of inflammatory pathways is a crucial factor contributing to the pathogenesis of seizures. In particular, the activation of interleukin-1 beta (IL-1β) system exerts proconvulsant effects in a large variety of seizure models. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein in the signaling cascade elicited by IL-1β. The present study aimed to investigate the expression pattern of MyD88 in rat models of seizures and in patients with refractory temporal lobe epilepsy (TLE), and to study the role of MyD88 in epileptic seizures. O...
Source: Experimental Neurology - May 18, 2017 Category: Neurology Authors: Wang N, Han X, Liu H, Zhao T, Li J, Feng Y, Mi X, Zhang Y, Chen Y, Wang X Tags: Exp Neurol Source Type: research

Cellular models as tools for the study of the role of alpha-synuclein in Parkinson's disease.
ro TF Abstract Neurodegenerative diseases are highly debilitating conditions characterised primarily by progressive neuronal loss and impairment of the nervous system. Parkinson's disease (PD) is one of the most common of these disorders, affecting 1-2% of the population above the age of 65. Although the underlying mechanisms of PD have been extensively studied, we still lack a full understanding of the molecular underpinnings of the disease. Thus, the in vitro and in vivo models currently used are able to only partially recapitulate the typical phenotypes of the disease. Here, we review various cell culture model...
Source: Experimental Neurology - May 16, 2017 Category: Neurology Authors: Lázaro DF, Pavlou MAS, Outeiro TF Tags: Exp Neurol Source Type: research

PPARgamma agonists rescue increased phosphorylation of FGF14 at S226 in the Tg2576 mouse model of Alzheimer's disease.
CONCLUSIONS: These results identify FGF14 as a potential PPARγ-sensitive target controlling Aβ-induced dysfunctions of neuronal activity in the DG underlying memory loss in early AD. PMID: 28522250 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 15, 2017 Category: Neurology Authors: Hsu WJ, Wildburger N, Haidacher SJ, Nenov MN, Folorunso O, Singh AK, Chesson BC, Franklin WF, Cortez I, Sadygov RG, Dineley KT, Rudra J, Taglialatela G, Lichti CF, Denner L, Laezza F Tags: Exp Neurol Source Type: research

Corrigendum to "The neuroprotective compound P7C3-A20 promotes neurogenesis and improves cognitive function after stroke" [Exp. Neurol. 290 (2017) 63-73].
Corrigendum to "The neuroprotective compound P7C3-A20 promotes neurogenesis and improves cognitive function after stroke" [Exp. Neurol. 290 (2017) 63-73]. Exp Neurol. 2017 May 13;: Authors: Loris ZB, Pieper AA, Dietrich WD PMID: 28511786 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 13, 2017 Category: Neurology Authors: Loris ZB, Pieper AA, Dietrich WD Tags: Exp Neurol Source Type: research

A method for isolating cortical interneurons sharing the same birthdays for gene expression studies.
Abstract The two neuronal populations in the cortex, pyramidal neurons and interneurons, can be separated based on neurotransmitter identity, however, within this segregation a large degree of diversity exists. Investigations into the molecular diversity of neurons are impeded by the inability to isolate cell populations born at different times for gene expression analysis. Developing interneurons may be distinguished by the expression of Glutamic Acid Decarboxylase-67 (GAD67). Neuronal birthdating using nucleoside analogs is an effective means of identifying coetaneous interneurons. Using these two features, neur...
Source: Experimental Neurology - May 13, 2017 Category: Neurology Authors: Ng HX, Lee EP, Cavanagh BL, Britto JM, Tan SS Tags: Exp Neurol Source Type: research

Functional connectivity alterations in a murine model of optic neuritis.
Abstract The basis for neuronal dysfunction following inflammatory demyelination of the central nervous system (CNS) remains poorly understood. We characterized the network response to white matter injury in the anterior visual pathway using an experimental model of optic neuritis (ON), as ON is often an early manifestation of immune-mediated CNS demyelination in multiple sclerosis (MS). Optical intrinsic signal imaging was performed before and after the induction of ON in mice to measure changes in cortical network functional connectivity. We observed a greater loss of connectivity between homotopic visual cortic...
Source: Experimental Neurology - May 11, 2017 Category: Neurology Authors: Wright PW, Archambault AS, Peek S, Bauer AQ, Culican SM, Ances BM, Culver JP, Wu GF Tags: Exp Neurol Source Type: research

Effects of hippocampal low-frequency stimulation in idiopathic non-human primate epilepsy assessed via a remote-sensing-enabled neurostimulator.
Abstract Individuals with pharmacoresistant epilepsy remain a large and under-treated patient population. Continued technologic advancements in implantable neurostimulators have spurred considerable research efforts directed towards the development of novel antiepileptic stimulation therapies. However, the lack of adequate preclinical experimental platforms has precluded a detailed understanding of the differential effects of stimulation parameters on neuronal activity within seizure networks. In order to chronically monitor seizures and the effects of stimulation in a freely-behaving non-human primate with idiopa...
Source: Experimental Neurology - May 7, 2017 Category: Neurology Authors: Wozny TA, Lipski WJ, Alhourani A, Kondylis ED, Antony A, Mark Richardson R Tags: Exp Neurol Source Type: research

Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors.
Abstract Capsaicin, the ingredient responsible for the pungent taste of hot chili peppers, is widely used in the study and management of pain. Recently, its neuroprotective effect has been described in multiple studies. Herein, we investigated the underlying mechanisms for the neuroprotective effect of capsaicin. Direct injection of capsaicin (1 or 3nmol) into the peri-infarct area reduced the infarct volume and improved neurological behavioral scoring and motor coordination function in the middle cerebral artery occlusion (MCAO)/reperfusion model in rats. The time window of the protective effect of capsaicin was ...
Source: Experimental Neurology - May 4, 2017 Category: Neurology Authors: Huang M, Cheng G, Tan H, Qin R, Zou Y, Wang Y, Zhang Y Tags: Exp Neurol Source Type: research

Effects of experimental traumatic brain injury and impaired glutamate transport on cortical spreading depression.
Abstract Cortical spreading depression (CSD) is associated with traumatic brain injury (TBI), stroke, migraines, and seizures. Typically, following TBIs and other insults, neuronal excitability in and around the area of the injury is affected, with reported increases in local glutamate signaling. Astrocytic glutamate transporters are critical for precise regulation of the extracellular glutamate availability. However, it remains unclear how impaired astrocytic glutamate transport or an acute TBI affect characteristics of the CSD. We quantified the properties of CSD using whole-cell and extracellular electrophysiol...
Source: Experimental Neurology - May 4, 2017 Category: Neurology Authors: Hosseini-Zare MS, Gu F, Abdulla A, Powell S, Žiburkus J Tags: Exp Neurol Source Type: research

The valproic acid-induced rodent model of autism.
Abstract Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children. Furthermore, rodents prenatally exposed to this drug display behavioral phenotypes characteristics ...
Source: Experimental Neurology - May 1, 2017 Category: Neurology Authors: Nicolini C, Fahnestock M Tags: Exp Neurol Source Type: research