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

Disruption of normal circadian clock function in a mouse model of tauopathy.
Abstract Disruption of normal circadian rhythm physiology is associated with neurodegenerative disease. In Alzheimer's disease (AD), circadian dysfunction has been attributed to β-amyloidosis. However, it is presently unclear whether tauopathy, another AD-associated neuropathology, also contributes to the disruption of normal circadian clock function. We demonstrate changes in normal circadian clock function in a transgenic mouse model of tauopathy (Tg4510) through assessment of both molecular and behavioral rhythms. We show that Tg4510 mice display a long free-running period at an age when tauopathy is prese...
Source: Experimental Neurology - April 28, 2017 Category: Neurology Authors: Stevanovic K, Yunus A, Joly-Amado A, Gordon M, Morgan D, Gulick D, Gamsby J Tags: Exp Neurol Source Type: research

Refining environmental enrichment to advance rehabilitation based research after experimental traumatic brain injury.
Abstract The typical environmental enrichment (EE) paradigm, which consists of continuous exposure after experimental traumatic brain injury (TBI), promotes behavioral and histological benefits. However, rehabilitation is often abbreviated in the clinic and administered in multiple daily sessions. While recent studies have demonstrated that a once daily 6-hr bout of EE confers benefits comparable to continuous EE, breaking the therapy into two shorter sessions may increase novelty and ultimately enhance recovery. Hence, the aim of the study was to test the hypothesis that functional and histological outcomes will ...
Source: Experimental Neurology - April 27, 2017 Category: Neurology Authors: Radabaugh HL, LaPorte MJ, Greene AM, Bondi CO, Lajud N, Kline AE Tags: Exp Neurol Source Type: research

Widespread cortical demyelination of both hemispheres can be induced by injection of pro-inflammatory cytokines via an implanted catheter in the cortex of MOG-immunized rats.
ister S Abstract Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats. After 14days the ra...
Source: Experimental Neurology - April 27, 2017 Category: Neurology Authors: Ücal M, Haindl MT, Adzemovic MZ, Strasser J, Theisl L, Zeitelhofer M, Kraitsy K, Ropele S, Schäfer U, Fazekas F, Hochmeister S Tags: Exp Neurol Source Type: research

Maternal IL-17A in autism.
Abstract Although autism spectrum disorder (ASD) has a strong genetic basis, its etiology is complex, with several genetic factors likely to be involved as well as environmental factors. Immune dysregulation has gained significant attention as a causal mechanism in ASD pathogenesis. ASD has been associated with immune abnormalities in the brain and periphery, including inflammatory disorders and autoimmunity in not only the affected individuals but also their mothers. Prenatal exposure to maternal immune activation (MIA) has been implicated as an environmental risk factor for ASD. In support of this notion, animal...
Source: Experimental Neurology - April 25, 2017 Category: Neurology Authors: Wong H, Hoeffer C Tags: Exp Neurol Source Type: research

Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion.
a ALR Abstract Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESCs/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal surv...
Source: Experimental Neurology - April 24, 2017 Category: Neurology Authors: Araújo MR, Kyrylenko S, Spejo AB, de Castro MV, Junior RSF, Barraviera B, de Oliveira ALR Tags: Exp Neurol Source Type: research

The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord injury.
Abstract Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI. To test this hypothesis,...
Source: Experimental Neurology - April 23, 2017 Category: Neurology Authors: Stivers NS, Pelisch N, Orem BC, Williams J, Nally JM, Stirling DP Tags: Exp Neurol Source Type: research

Altered somatosensory cortex neuronal activity in a rat model of Parkinson's disease and levodopa-induced dyskinesias.
In this study, we explored the neuronal firing activity of excitatory pyramidal cells and inhibitory interneurons in the forelimb region of the primary somatosensory cortex (S1FL-Ctx), along with its interaction with oscillatory activity of the primary motor cortex (MCtx) in 6-hydroxydopamine lesioned hemiparkinsonian (HP) and levodopa-primed dyskinetic (HP-LID) rats as compared to controls under urethane (1.4g/kg, i.p.) anesthesia. Further, gene expression patterns of distinct markers for inhibitory GABAergic neurons were analyzed in both cortical regions. While firing frequency and burst activity of S1FL-Ctx inhibitory i...
Source: Experimental Neurology - April 23, 2017 Category: Neurology Authors: Alam M, Rumpel R, Jin X, von Wrangel C, Tschirner S, Krauss JK, Grothe C, Ratzka A, Schwabe K Tags: Exp Neurol Source Type: research

Trumping neurodegeneration: Targeting common pathways regulated by autosomal recessive Parkinson's disease genes.
Abstract Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Most PD cases are sporadic; however, rare familial forms have been identified. Autosomal recessive PD (ARPD) results from mutations in Parkin, PINK1, DJ-1, and ATP13A2, while rare, atypical juvenile ARPD result from mutations in FBXO7, DNAJC6, SYNJ1, and PLA2G6. Studying these genes and their function has revealed mitochondrial quality control, protein degradation processes, and oxidative stress responses as common pathways underlying PD pathogenesis. Understanding how aber...
Source: Experimental Neurology - April 23, 2017 Category: Neurology Authors: Scott L, Dawson VL, Dawson TM Tags: Exp Neurol Source Type: research

Worms on the spectrum - C. elegans models in autism research.
Abstract The small non-parasitic nematode Caenorhabditis elegans is widely used in neuroscience thanks to its well-understood development and lineage of the nervous system. Furthermore, C. elegans has been used to model many human developmental and neurological conditions to better understand disease mechanisms and identify potential therapeutic strategies. Autism spectrum disorder (ASD) is the most prevalent of all neurodevelopmental disorders, and the C. elegans system may provide opportunities to learn more about this complex disorder. Along with a repertoire of behaviours, since basic cell biology and biochemi...
Source: Experimental Neurology - April 20, 2017 Category: Neurology Authors: Schmeisser K, Alex Parker J Tags: Exp Neurol Source Type: research

Supraspinal respiratory plasticity following acute cervical spinal cord injury.
Abstract Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the diaphragm - a primary muscle of respiration. Consequently, people with cervical level injuries often become dependent on assisted ventilation and are susceptible to secondary complications. However, there is mounting evidence for limited spontaneous recovery of respiratory function following injury, demonstrating the neuroplastic potential of respiratory networks. Although many studies have shown such plasticity at the level of the spinal cor...
Source: Experimental Neurology - April 19, 2017 Category: Neurology Authors: Bezdudnaya T, Marchenko V, Zholudeva LV, Spruance VM, Lane MA Tags: Exp Neurol Source Type: research

Role of the locus coeruleus catecholaminergic neurons in the chemosensory control of breathing in a Parkinson's disease model.
Abstract A previous study has demonstrated that in the 6-hydroxydopamine (6-OHDA)-model of Parkinson's disease (PD) there is a reduction in the number of Phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia 40days after PD-induction. The functional deficiency is restored 60days after 6-OHDA injection and here we tested the hypothesis that the locus coeruleus (LC) could be a candidate to restore the breathing deficiency. Minute Ventilation (VE) in response to hypercapnia (7% CO2) was assessed one day before, and then 40 and 60days after bilateral 6-OHDA (24&mu...
Source: Experimental Neurology - April 18, 2017 Category: Neurology Authors: Oliveira LM, Tuppy M, Moreira TS, Takakura AC Tags: Exp Neurol Source Type: research

Mice with conditional NeuroD1 knockout display reduced aberrant hippocampal neurogenesis but no change in epileptic seizures.
Abstract Adult neurogenesis is significantly increased in the hippocampus of rodent models of temporal lobe epilepsy (TLE). These adult-generated neurons have recently been shown to play a contributing role in the development of spontaneous recurrent seizures (SRS). In order to eventually target pro-epileptic adult neurogenesis in the clinical setting, it will be important to identify molecular players involved in the control of aberrant neurogenesis after seizures. Here, we focused on NeuroD1 (ND1), a member of the bHLH family of transcription factors previously shown to play an essential role in the differentiat...
Source: Experimental Neurology - April 18, 2017 Category: Neurology Authors: Brulet R, Zhu J, Aktar M, Hsieh J, Cho KO Tags: Exp Neurol Source Type: research

Inflammation-induced GluA1 trafficking and membrane insertion of Ca(2+) permeable AMPA receptors in dorsal horn neurons is dependent on spinal tumor necrosis factor, PI3 kinase and protein kinase A.
Abstract Peripheral inflammation induces sensitization of nociceptive spinal cord neurons. Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca(2+) permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant pain behavior, molecular mechanisms connecting these two events have not been studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected rats compared to controls. In the same tissue, GluA...
Source: Experimental Neurology - April 12, 2017 Category: Neurology Authors: Wigerblad G, Huie JR, Yin HZ, Leinders M, Pritchard RA, Koehrn FJ, Xiao WH, Bennett GJ, Huganir RL, Ferguson AR, Weiss JH, Svensson CI, Sorkin LS Tags: Exp Neurol Source Type: research

Hypersociability in the Angelman syndrome mouse model.
We report that mice with maternally-inherited Ube3a gene deletion (Ube3a(mKO)) have a prolonged preference for, and interaction with, social stimuli in the three chamber social approach task. By contrast, interactions with a novel object are reduced. Further, ultrasonic vocalizations and physical contacts are increased in male and female Ube3a(mKO) mice paired with an unfamiliar genotype-matched female. Single housing wild type mice increased these same social behavior parameters to levels observed in Ube3a(mKO) mice where this effect was partially occluded. These results indicate sociability is repressed by social experie...
Source: Experimental Neurology - April 11, 2017 Category: Neurology Authors: Stoppel DC, Anderson MP Tags: Exp Neurol Source Type: research