Novel p75 neurotrophin receptor ligand stabilizes neuronal calcium, preserves mitochondrial movement and protects against HIV associated neuropathogenesis.
Abstract Human immunodeficiency virus (HIV) rapidly penetrates into the brain and establishes a persistent infection of macrophages/microglia. Activation of these cells by HIV results in the secretion of soluble factors that destabilize neuronal calcium homeostasis, encourage oxidative stress and result in neural damage. This damage is thought to underlie the cognitive-motor dysfunction that develops in many HIV-infected patients. Studies have suggested that neurotrophins may protect neurons from the toxic effects of HIV-associated proteins. To better understand the pathogenic mechanisms and the neuroprotective po...
Source: Experimental Neurology - September 27, 2015 Category: Neurology Authors: Meeker RB, Poulton W, Clary G, Schriver M, Longo FM Tags: Exp Neurol Source Type: research

Altered terminal Schwann cell morphology precedes denervation in SOD1 mice.
In this study, an analysis of TSC morphology and number was performed in relation to NMJ innervation status in mice which express the G93A SOD1 mutation. At P30, all NMJs of the fast medial gastrocnemius (MG) muscle were fully innervated by a single motor axon but 50% of NMJs lacked TSC cell bodies and were instead covered by the processes of Schwann cells with cell bodies located on the preterminal axons. NMJs in P30 slow soleus muscles were also fully innervated by single motor axons and only 5% of NMJs lacked a TSC cell body. At P60, about 25% of MG NMJs were denervated and lacked labeling for TSCs while about 60% of in...
Source: Experimental Neurology - September 25, 2015 Category: Neurology Authors: Carrasco DI, Seburn KL, Pinter MJ Tags: Exp Neurol Source Type: research

An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior.
Abstract Understanding the role of SCN8A in epilepsy and behavior is critical in light of recently identified human SCN8A epilepsy mutations. We have previously demonstrated that Scn8a(med) and Scn8a(med-jo) mice carrying mutations in the Scn8a gene display increased resistance to flurothyl and kainic acid-induced seizures; however, they also exhibit spontaneous absence seizures. To further investigate the relationship between altered SCN8A function and epilepsy, we introduced the SCN1A-R1648H mutation, identified in a family with generalized epilepsy with febrile seizures plus (GEFS+), into the corresponding posi...
Source: Experimental Neurology - September 24, 2015 Category: Neurology Authors: Makinson CD, Dutt K, Lin F, Papale LA, Shankar A, Barela AJ, Liu R, Goldin AL, Escayg A Tags: Exp Neurol Source Type: research

Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways.
In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control L4-L5 DRGs tre...
Source: Experimental Neurology - September 22, 2015 Category: Neurology Authors: Zheng G, Hong S, Hayes JM, Wiley JW Tags: Exp Neurol Source Type: research

Riluzole promotes motor and respiratory recovery associated enhanced neuronal survival and function following high cervical hemisection.
In conclusion, using a C2 hemisection injury model, this study provides novel evidence of motoneuron loss caudal to the injury and supports riluzole's capacity to promote neuronal preservation and function of neural network caudal to the SCI resulting in early and sustained functional improvements. PMID: 26394202 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 19, 2015 Category: Neurology Authors: Satkunendrarajah K, Nissiri F, Karadimas SK, Lip A, Yao G, Fehlings MG Tags: Exp Neurol Source Type: research

Thrombin decreases expression of the glutamate transporter GLAST and inhibits glutamate uptake in primary cortical astrocytes via the rho kinase pathway.
Abstract Astrocyte glutamate transporters GLAST and GLT1 play a key role in regulating neuronal excitation and their levels are altered in patients with epilepsy, and after traumatic brain injury. The mechanisms which regulate their expression are not well understood. We tested the hypothesis that exposure of astrocytes to high levels of thrombin, as may occur after compromise of the blood-brain barrier, would reduce astrocyte glutamate transporter levels. In isolated rat cortical astrocytes we examined the effects of thrombin on the expression and function of glutamate transporters, and the signaling pathways inv...
Source: Experimental Neurology - September 18, 2015 Category: Neurology Authors: Piao C, Ranaivo HR, Rusie A, Wadhwani N, Koh S, Wainwright MS Tags: Exp Neurol Source Type: research

The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity.
Abstract The hyaluronan and proteoglycanbinding link protein (Hapln) is a key molecule in the formation and control of hyaluronan-based condensed perineuronal matrix in the adult brain. This review summarizes the recent advances in understanding the role of Haplns in formation and control of two distinct types of perineuronal matrices, one for "classical" PNN and the other for the specialized extracellular matrix (ECM) at the node of Ranvier in the central nervous system (CNS). We introduce the structural components of each ECM organization including the basic concept of supramolecular structure named &q...
Source: Experimental Neurology - September 17, 2015 Category: Neurology Authors: Oohashi T, Edamatsu M, Bekku Y, Carulli D Tags: Exp Neurol Source Type: research

Newly Generated Neurons at 2 Months Post-Status Epilepticus Are Functionally Integrated into Neuronal Circuitry in Mouse Hippocampus (Abbreviated title: Neurogenesis in Chronically Epileptic Hippocampus).
Abstract Emerging evidence has linked chronic temporal lobe epilepsy to dramatically reduced neurogenesis in the dentate gyrus. However, the profile of different components of neurogenesis in the chronically epileptic hippocampus is still unclear, especially the incorporation of newly generated cells. To address the issue, newly generated cells in the sub-granular zone of the dentate gyrus were labeled by the proliferation marker Bromodeoxyuridine (BrdU) or Retroviral Vector Expressing Green Fluorescent Protein 2months after pilocarpine-induced status epilepticus. The newly generated neurons that extended axons to...
Source: Experimental Neurology - September 15, 2015 Category: Neurology Authors: Hu M, Zhu K, Chen XL, Zhang YJ, Zhang JS, Xiao XL, Liu JX, Liu Y Tags: Exp Neurol Source Type: research

Phosphorylation of TRPV1 by Cyclin-dependent kinase 5 promotes TRPV1 surface localization, leading to inflammatory thermal hyperalgesia.
Abstract Cyclin-dependent kinase 5 (Cdk5) is an important serine/threonine kinase that plays critical roles in many physiological processes. Recently, Cdk5 has been reported to phosphorylate TRPV1 at threonine 407 (Thr-407) in humans (Thr-406 in rats), which enhances the function of TRPV1 channel and promotes thermal hyperalgesia in the complete Freund's adjuvant (CFA)-induced inflammatory pain rats. However, the underlying mechanisms are still unknown. Here, we demonstrate that Cdk5 phosphorylates TRPV1 at Threonine 406 and promotes the surface localization of TRPV1, leading to inflammatory thermal hyperalgesia. ...
Source: Experimental Neurology - September 12, 2015 Category: Neurology Authors: Liu J, Du J, Yang Y, Wang Y Tags: Exp Neurol Source Type: research

Bulleyaconitine A depresses neuropathic pain and potentiation at C-fiber synapses in spinal dorsal horn induced by paclitaxel in rats.
Abstract Paclitaxel, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and at present no effective drug is available for treatment of the serious side effect. Here, we tested if intragastrical application of bulleyaconitine A (BLA), which has been approved for clinical treatment of chronic pain in China since 1985, could relieve the paclitaxel-induced neuropathic pain. A single dose of BLA attenuated the mechanical allodynia, thermal hyperalgesia induced by paclitaxel dose-dependently. Repetitive administration of the drug (0.4 and 0.8mg/kg, t.i.d. for 7 d) during or after paclitaxe...
Source: Experimental Neurology - September 12, 2015 Category: Neurology Authors: Zhu HQ, Xu J, Shen KF, Pang RP, Wei XH, Liu XG Tags: Exp Neurol Source Type: research

Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI.
Abstract Hypoxia-ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the develo...
Source: Experimental Neurology - September 12, 2015 Category: Neurology Authors: Waddell J, Hanscom M, Shalon Edwards N, McKenna MC, McCarthy MM Tags: Exp Neurol Source Type: research

Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes.
e; JD Abstract Insufficient regeneration of central nervous system (CNS) axons contributes to persisting neurological dysfunction after spinal cord injury (SCI). Peripheral nerve grafts (PNGs) support regeneration by thousands of injured intraspinal axons and help them bypass some of the extracellular barriers that form after SCI. However this number represents but a small portion of the total number of axons that are injured. Here we tested if rhythmic sensory stimulation during cycling exercise would boost the intrinsic regenerative state of neurons to enhance axon regeneration into PNGs after a lower thoracic (...
Source: Experimental Neurology - September 11, 2015 Category: Neurology Authors: Sachdeva R, Theisen CC, Ninan V, Twiss JL, Houlé JD Tags: Exp Neurol Source Type: research

Depressive-like phenotype induced by AAV-mediated overexpression of human α-synuclein in midbrain dopaminergic neurons.
This study demonstrates that AAV-mediated α-synuclein overexpression in dopamine neurons is not only useful to model motor impairments of PD, but also depression. This study also provides evidence that depression in experimental Parkinsonism is correlated to dysregulation of the HPA axis and to alterations in proteins involved in synaptic plasticity. PMID: 26363495 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 9, 2015 Category: Neurology Authors: Caudal D, Alvarsson A, Björklund A, Svenningsson P Tags: Exp Neurol Source Type: research

(R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model.
Abstract Mutations of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN ...
Source: Experimental Neurology - September 9, 2015 Category: Neurology Authors: Weng YH, Chen CY, Lin KJ, Chen YL, Yeh TH, Hsiao IT, Chen IJ, Lu CS, Wang HL Tags: Exp Neurol Source Type: research

Microglia in the TBI brain: The good, the bad, and the dysregulated.
Abstract As the major cellular component of the innate immune system in the central nervous system (CNS) and the first line of defense whenever injury or disease occurs, microglia play a critical role in neuroinflammation following a traumatic brain injury (TBI). In the injured brain microglia can produce neuroprotective factors, clear cellular debris and orchestrate neurorestorative processes that are beneficial for neurological recovery after TBI. However, microglia can also become dysregulated and can produce high levels of pro-inflammatory and cytotoxic mediators that hinder CNS repair and contribute to neuron...
Source: Experimental Neurology - September 2, 2015 Category: Neurology Authors: Loane DJ, Kumar A Tags: Exp Neurol Source Type: research

A meta-analysis of efficacy in pre-clinical human stem cell therapies for traumatic brain injury.
CONCLUSIONS: Although human cell therapy studies report improved behavioral outcomes in the majority of preclinical literature, the methods are too heterogeneous to facilitate direct comparisons and bias was detected. Replication and standardization are needed to identify procedural variables to yield the best results. We encourage the use of quality criteria and rigor for future studies of human cell therapy in animal models of TBI. PMID: 26342754 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 2, 2015 Category: Neurology Authors: Chang J, Phelan M, Cummings BJ Tags: Exp Neurol Source Type: research

The role of CNS TLR2 activation in mediating innate versus adaptive neuroinflammation.
We examined the effects of intra-cerebro-ventricular (ICV) injection of Zymosan, a TLR2 agonist, on naive versus EAE animals. The neuro-inflammatory response was characterized by immune-fluorescent staining for IBA-1+ microglia/ macrophages and CD3+ T cells, and by semi-quantitative real time PCR for TLR2 and immune cytokines. The nature of the immune cells isolated from EAE brain tissue was assessed by their proliferative response to the PLP peptide autoantigen. Survival and clinical scores were monitored; demyelination and axonal loss were quantified by gold-black and Bielschowsky stains. Our findings showed that Zymosan...
Source: Experimental Neurology - September 2, 2015 Category: Neurology Authors: Luz A, Fainstein N, Einstein O, Ben-Hur T Tags: Exp Neurol Source Type: research

Neonatal hypoxia-ischemia impairs juvenile recognition memory by disrupting the maturation of prefrontal-hippocampal networks.
PMID: 26341391 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 1, 2015 Category: Neurology Authors: Domnick NK, Gretenkord S, De Feo V, Sedlacik J, Brockmann MD, Hanganu-Opatz IL Tags: Exp Neurol Source Type: research

LY395756, an mGluR2 agonist and mGluR3 antagonist, enhances NMDA receptor expression and function in the normal adult rat prefrontal cortex, but fails to improve working memory and reverse MK801-induced working memory impairment.
Abstract Targeting group II metabotropic glutamate receptors (mGluR2/3) has been proposed to correct the dysfunctional glutamatergic system, particularly NMDA receptor (NMDAR) hypofunction, for treatment of schizophrenia. However, how activation of mGluR2/3 affects NMDAR function in adult animals remains elusive. Here we show the effects of LY395756 (LY39), a compound acting as both an mGluR2 agonist and mGluR3 antagonist, on the NMDAR expression and function of normal adult rat prefrontal cortex (PFC) as well as working memory function in the MK801 model of schizophrenia. We found that in vivo administration of L...
Source: Experimental Neurology - September 1, 2015 Category: Neurology Authors: Li ML, Yang SS, Xing B, Ferguson BR, Gulchina Y, Li YC, Li F, Hu XQ, Gao WJ Tags: Exp Neurol Source Type: research

The proinflammatory cytokine, interleukin-17A, augments mitochondrial function and neurite outgrowth of cultured adult sensory neurons derived from normal and diabetic rats.
Abstract BACKGROUND: Diabetic neuropathy comprises dying back of nerve endings that reflects impairment in axonal plasticity and regenerative nerve growth. Metabolic changes in diabetes can lead to a dysregulation of hormonal mediators, such as cytokines, that may constrain distal nerve fiber growth. Interleukin-17 (IL-17A), a proinflammatory and neurotropic cytokine produced by T-cells, was significantly reduced in sciatic nerve of streptozotocin (STZ)-diabetic rats. Thus we studied the effect of interleukin-17A (IL-17A), a proinflammatory and neurotropic cytokine produced by T-cells, on the phenotype of sensory ...
Source: Experimental Neurology - August 27, 2015 Category: Neurology Authors: Habash T, Saleh A, Roy Chowdhury SK, Smith DR, Fernyhough P Tags: Exp Neurol Source Type: research

Sugar-Dependent Modulation of Neuronal Development, Regeneration, and Plasticity by Chondroitin Sulfate Proteoglycans.
Abstract Chondroitin sulfate proteoglycans (CSPGs) play important roles in the developing and mature nervous system, where they guide axons, maintain stable connections, restrict synaptic plasticity, and prevent axon regeneration following CNS injury. The chondroitin sulfate glycosaminoglycan (CS GAG) chains that decorate CSPGs are essential for their functions. Through these sugar chains, CSPGs are able to bind and regulate the activity of a diverse range of proteins. CSPGs have been found both to promote and inhibit neuronal growth. They can promote neurite outgrowth by binding to various growth factors such as ...
Source: Experimental Neurology - August 24, 2015 Category: Neurology Authors: Miller GM, Hsieh-Wilson LC Tags: Exp Neurol Source Type: research

Evidence for accelerated tauopathy in the retina of transgenic P301S tau mice exposed to repetitive mild traumatic brain injury.
In this study, we exposed mice harboring the tau P301S transgene associated with FTD to repetitive mTBI schedules by impact acceleration (IA) that we have previously characterized. We explored the progression of tauopathy in the retina and neocortex based on density of neuronal profiles loaded with tau pS422, a marker of advanced tau hyperphosphorylation. We found that the density of tau pS422 (+) retinal ganglion cells (RGCs) increased twenty fold with one mTBI hit, a little over fifty fold with four mTBI hits and sixty fold with 12 mTBI hits. The severity of mTBI burden (number of hits) was a significant factor in tauopa...
Source: Experimental Neurology - August 23, 2015 Category: Neurology Authors: Xu L, Ryu J, Nguyen JV, Arena J, Rha E, Vranis P, Hitt D, Marsh-Armstrong N, Koliatsos VE Tags: Exp Neurol Source Type: research

Melanocortin receptor agonist ACTH 1-39 protects rat forebrain neurons from apoptotic, excitotoxic and inflammation-related damage.
Abstract Patients with relapsing remitting multiple sclerosis (RRMS) are commonly treated with high doses of intravenous corticosteroids (CS). ACTH 1-39, a member of the melanocortin family, stimulates production of CS by the adrenals, but melanocortin receptors are also found in the central nervous system (CNS) and on immune cells. ACTH is produced within the CNS and may have direct protective effects on glia and neurons independent of CS. We previously reported that ACTH 1-39 protected oligodendroglia (OL) and their progenitors (OPC) from a panel of excitotoxic and inflammation-related agents. Neurons are the mo...
Source: Experimental Neurology - August 20, 2015 Category: Neurology Authors: Lisak RP, Nedelkoska L, Bealmear B, Benjamins JA Tags: Exp Neurol Source Type: research

Protective effects of Ndfip1 on MPP(+)-induced apoptosis in MES23.5 cells and its underlying mechanisms.
Abstract Apoptosis has been implicated as one of the important mechanisms involved in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Increasing evidence suggested that Ndfip1 was a neuroprotective protein, and Ndfip1-mediated protein ubiquitination might be a possible survival strategy in neuronal injury. The aim of the present study is to investigate the neuroprotective effect of Ndfip1 on 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells and the underlying mechanisms. Results showed that overexpression of Ndfip1 could significantly attenuate MPP(+)-induced cell loss and nuclear co...
Source: Experimental Neurology - August 20, 2015 Category: Neurology Authors: Liu K, Xu H, Xiang H, Sun P, Xie J Tags: Exp Neurol Source Type: research

Apoptotic neurons induce proliferative responses of progenitor cells in the postnatal neocortex.
Abstract Apoptotic cell death is the leading cause of neuronal loss after neonatal brain injury. Little is known about the intrinsic capacity of the immature cerebral cortex for replacing dead cells. Here we test the hypothesis that neuronal apoptosis is able to trigger compensatory proliferation in surrounding cells. In order to establish a "pure" apoptotic cell death model and to avoid the confounding effects of broken blood-brain barrier and inflammatory reactions, we used a diphtheria toxin (DT) and diphtheria toxin receptor (DTR) system to induce ablation of layer IV neurons in the rodent somatosens...
Source: Experimental Neurology - August 17, 2015 Category: Neurology Authors: Petrenko V, Mihhailova J, Salmon P, Kiss JZ Tags: Exp Neurol Source Type: research

Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS.
Abstract Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plastic...
Source: Experimental Neurology - August 16, 2015 Category: Neurology Authors: Nichols NL, Satriotomo I, Harrigan DJ, Mitchell GS Tags: Exp Neurol Source Type: research

Intracellular and extracellular O-linked N-acetylglucosamine in the nervous system.
Abstract Addition of O-linked N-acetylglucosamine (O-GlcNAc) to the hydroxyl group of serine and threonine residues (O-GlcNAcylation) is a post-translational modification common to multicellular eukaryotes. To date, O-GlcNAcylations have been divided into two categories: the first involves nucleocytoplasmic and mitochondrial (intracellular) O-GlcNAcylation catalyzed by O-GlcNAc transferase (OGT), and the second involves O-GlcNAcylation in the secretory pathways (extracellular) catalyzed by epidermal growth factor (EGF) domain-specific O-GlcNAc transferase (EOGT). Intracellular O-GlcNAcylation is involved in essent...
Source: Experimental Neurology - August 13, 2015 Category: Neurology Authors: Ogawa M, Sawaguchi S, Kamemura K, Okajima T Tags: Exp Neurol Source Type: research

"GAG-ing with the neuron": The role of glycosaminoglycan patterning in the central nervous system.
"GAG-ing with the neuron": The role of glycosaminoglycan patterning in the central nervous system. Exp Neurol. 2015 Aug 12; Authors: Smith PD, Coulson-Thomas VJ, Foscarin S, Kwok JC, Fawcett JW Abstract Proteoglycans (PGs) are a diverse family of proteins that consist of one or more glycosaminoglycan (GAG) chains, covalently linked to a core protein. PGs are major components of the extracellular matrix (ECM) and play critical roles in development, normal function and damage-response of the central nervous system (CNS). GAGs are classified based on their disaccharide subunits, into the follow...
Source: Experimental Neurology - August 12, 2015 Category: Neurology Authors: Smith PD, Coulson-Thomas VJ, Foscarin S, Kwok JC, Fawcett JW Tags: Exp Neurol Source Type: research

Combination Therapy with Lenalidomide and Nanoceria Ameliorates CNS Autoimmunity.
Abstract OBJECTIVE: Multiple sclerosis (MS) is a debilitating neurological disorder involving an autoimmune reaction to oligodendrocytes and degeneration of the axons they ensheath in the CNS. Because the damage to oligodendrocytes and axons involves local inflammation and associated oxidative stress, we tested the therapeutic efficacy of combined treatment with a potent anti-inflammatory thalidomide analog (lenalidomide) and novel synthetic anti-oxidant cerium oxide nanoparticles (nanoceria) in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. METHODS: C57BL/6 mice were randomly assigned...
Source: Experimental Neurology - August 12, 2015 Category: Neurology Authors: Eitan E, Hutchison ER, Greig NH, Tweedie D, Celik H, Ghosh S, Fishbein KW, Spencer RG, Sasaki CY, Ghosh P, Das S, Chigurapati S, Raymick J, Sarkar S, Chigurupati S, Seal S, Mattson MP Tags: Exp Neurol Source Type: research

Requirement of keratan sulfate proteoglycan phosphacan with a specific sulfation pattern for critical period plasticity in the visual cortex.
Abstract Proteoglycans play important roles in regulating the development and functions of the brain. They consist of a core protein and glycosaminoglycans, which are long sugar chains of repeating disaccharide units with sulfation. A recent study demonstrated that the sulfation pattern of chondroitin sulfate on proteoglycans contributes to regulation of the critical period of experience-dependent plasticity in the mouse visual cortex. In the present study, we investigated the role of keratan sulfate (KS), another glycosaminoglycan, in critical period plasticity in the mouse visual cortex. Immunohistochemical anal...
Source: Experimental Neurology - August 12, 2015 Category: Neurology Authors: Takeda-Uchimura Y, Uchimura K, Sugimura T, Yanagawa Y, Kawasaki T, Komatsu Y, Kadomatsu K Tags: Exp Neurol Source Type: research

Activation of glucocorticoid receptors in Müller glia is protective to retinal neurons and suppresses microglial reactivity.
Activation of glucocorticoid receptors in Müller glia is protective to retinal neurons and suppresses microglial reactivity. Exp Neurol. 2015 Aug 10; Authors: Gallina D, Zelinka CP, Cebulla C, Fischer AJ Abstract Reactive microglia and macrophages are prevalent in damaged retinas. Glucocorticoid signaling is known to suppress inflammation and the reactivity of microglia and macrophages. In the vertebrate retina, the glucocorticoid receptor (GCR) is known to be activated and localized to the nuclei of Müller glia (Gallina et al., 2014). Accordingly, we investigated how signaling through GCR i...
Source: Experimental Neurology - August 10, 2015 Category: Neurology Authors: Gallina D, Zelinka CP, Cebulla C, Fischer AJ Tags: Exp Neurol Source Type: research

Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca(2+) channels.
Abstract Our previous studies revealed that L-type voltage-dependent Ca(2+) channels (Cav1.2L-VDCCs) are modulated by the neural extracellular matrix backbone, polyanionic glycan hyaluronic acid. Here we used isothermal titration calorimetry and screened a set of peptides derived from the extracellular domains of Cav1.2α1 to identify putative binding sites between the channel and hyaluronic acid or another class of polyanionic glycans, heparin/heparan sulfates. None of the tested peptides showed detectable interaction with hyaluronic acid, but two peptides derived from the first pore-forming domain of Cav1.2...
Source: Experimental Neurology - August 10, 2015 Category: Neurology Authors: Garau G, Magotti P, Heine M, Korotchenko S, Lievens PM, Berezin V, Dityatev A Tags: Exp Neurol Source Type: research

Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord injury.
Abstract Macrophages with different activation states are present after spinal cord injury (SCI). M1 macrophages purportedly promote secondary injury processes while M2 cells support axon growth. The average age at the time of SCI has increased in recent decades, however, little is known about how different physiological factors contribute to macrophage activation states after SCI. Here we investigate the effect of age on IL-10, a key indicator of M2 macrophage activation. Following mild-moderate SCI in 4 and 14month old (MO) mice we detected significantly reduced IL-10 expression with age in the injured spinal co...
Source: Experimental Neurology - August 8, 2015 Category: Neurology Authors: Zhang B, Bailey WM, Braun KJ, Gensel JC Tags: Exp Neurol Source Type: research

Studying Polyglutamine Diseases in Drosophila.
Abstract Polyglutamine (polyQ) diseases are a family of dominantly transmitted neurodegenerative disorders caused by an abnormal expansion of CAG trinucleotide repeats in the protein-coding regions of the respective disease-causing genes. Despite their simple genetic basis, the etiology of these diseases is far from clear. Over the past two decades, Drosophila has proven to be successful in modeling this family of neurodegenerative disorders, including the faithful recapitulation of pathological features such as polyQ length-dependent formation of protein aggregates and progressive neuronal degeneration. Additiona...
Source: Experimental Neurology - August 6, 2015 Category: Neurology Authors: Xu Z, Tito A, Rui YN, Zhang S Tags: Exp Neurol Source Type: research

T-type calcium channels contribute to calcium disturbances in brain during hyponatremia.
This study examined the amplitude, timing, and mechanism of these surprising calcium changes. We also tested whether hyponatremia increased calcium entry into brain cells or calcium binding to chondroitin sulfate (CS), a negatively charged constituent of the extracellular matrix (ECM) that may be occupied by sodium during normonatremia. We report three major findings. First we show that CS does not contribute to extracellular calcium changes during low-NaCl treatments. Second, we show that the time to minimum extracellular calcium during low-NaCl treatment is significantly shorter than the time to maximum extracellular cal...
Source: Experimental Neurology - August 6, 2015 Category: Neurology Authors: Odackal J, Sherpa AD, Patel N, Colbourn R, Hrabetova S Tags: Exp Neurol Source Type: research

Post-stroke transplantation of adult subventricular zone derived neural progenitor cells - a comprehensive analysis of cell delivery routes and their underlying mechanisms.
DM Abstract With neuroprotective approaches having failed until recently, current focus on experimental stroke research has switched towards manipulation of post-ischemic neuroregeneration. Transplantation of subventricular zone (SVZ) derived neural progenitor cells (NPCs) is a promising strategy for promotion of neurological recovery. Yet, fundamental questions including the optimal cell delivery route still have to be addressed. Consequently, male C57BL6 mice were exposed to transient focal cerebral ischemia and allowed to survive for as long as 84days post-stroke. At six hours post-stroke, NPCs were grafted us...
Source: Experimental Neurology - August 4, 2015 Category: Neurology Authors: Doeppner TR, Kaltwasser B, Teli MK, Sanchez-Mendoza EH, Kilic E, Bähr M, Hermann DM Tags: Exp Neurol Source Type: research

A Balanced View of the Cerebrospinal Fluid Composition and Functions: Focus on Adult Humans.
Abstract In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of th...
Source: Experimental Neurology - August 3, 2015 Category: Neurology Authors: Spector R, Robert Snodgrass S, Johanson CE Tags: Exp Neurol Source Type: research

Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.
Abstract Parkinson's disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain. Symptomatic therapies are available but no treatment slows or prevents the loss of neurons. Neuroinflammation has been implicated in its pathogenesis. To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients. Herein, the ...
Source: Experimental Neurology - August 2, 2015 Category: Neurology Authors: Mounsey RB, Mustafa S, Robinson L, Ross RA, Riedel G, Pertwee RG, Teismann P Tags: Exp Neurol Source Type: research

Suppression of spreading depolarization and stabilization of dendritic spines by GLYX-13, an NMDA receptor glycine-site functional partial agonist.
Abstract Cortical spreading depolarization (SD) is a slow self-propagating wave of mass cellular depolarization in brain tissue, thought to be the underlying cause of migraine scintillating scotoma and aura, and associated with stroke, traumatic brain injury, and termination of status epilepticus. The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR), which gates influx of calcium and is an important trigger of long-term synaptic plasticity, is also a contributor to the initiation and propagation of SD. The current study tested the potential of pharmacological modulation of NMDAR activity through the obli...
Source: Experimental Neurology - August 2, 2015 Category: Neurology Authors: Zhang XL, Shuttleworth CW, Moskal JR, Stanton PK Tags: Exp Neurol Source Type: research

Editorial: Special issue on standardization of preclinical evaluation of animal models for myasthenia gravis.
PMID: 26071136 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - June 15, 2015 Category: Neurology Authors: Kusner LL, Kaminski HJ Tags: Exp Neurol Source Type: research

Chronic inhibitory effect of riluzole on trophic factor production.
ez AG Abstract Riluzole is the only FDA approved drug for the treatment of amyotrophic lateral sclerosis (ALS). However, the drug affords moderate protection to ALS patients, extending life for a few months by a mechanism that remains controversial. In the presence of riluzole, astrocytes increase the production of factors protective to motor neurons. The stimulation of trophic factor production by motor neuron associated cells may contribute to riluzole's protective effect in ALS. Here, we investigated the effects of media conditioned by astrocytes and Schwann cells acutely or chronically incubated with riluzole ...
Source: Experimental Neurology - June 10, 2015 Category: Neurology Authors: Dennys CN, Armstrong J, Levy M, Byun YJ, Ramdial KR, Bott M, Rossi FH, Fernández-Valle C, Franco MC, Estevez AG Tags: Exp Neurol Source Type: research

Entorhinal Cortex Lesions Result In Adenosine-Sensitive High Frequency Oscillations In The Hippocampus.
rez R Abstract Entorhinal cortex (EC) projections to the hippocampus run along the perforant path and activate the hippocampal area CA3 and the dentate gyrus (DG), which, in turn, drives CA3. Because cortical trauma damages the source of inputs to the hippocampus, we hypothesize that such an event can be reflected in immediate alterations of the hippocampal oscillatory activity. We here explore whether acute, localized disruption of EC-EC connectivity is involved in the generation or modulation of high frequency oscillations (HFO) in the hippocampus. We conducted in vitro electrophysiological recordings in CA3 and...
Source: Experimental Neurology - June 10, 2015 Category: Neurology Authors: Ortiz F, Gutiérrez R Tags: Exp Neurol Source Type: research

Evaluation of the anatomical and functional consequences of repetitive mild cervical contusion using a model of spinal concussion.
Abstract Spinal cord concussion is characterized by a transient loss of motor and sensory function that generally resolves without permanent deficits. Spinal cord concussions usually occur during vehicular accidents, falls, and sport activity, but unlike brain concussions, have received much less attention despite the potential for repeated injury leading to permanent neurological sequelae. Consequently, there is no consensus regarding decisions related to return to play following an episode of spinal concussion, nor an understanding of the short- and long-term consequences of repeated injury. Importantly, there a...
Source: Experimental Neurology - June 9, 2015 Category: Neurology Authors: Jin Y, Bouyer J, Haas C, Fischer I Tags: Exp Neurol Source Type: research

Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men.
Abstract Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent retrospective case series published over the last decade on athletes and military personnel have added considerably to our clinical and histopathological knowledge of CTE. This has marked a vital turning point in the traumatic brain injury (TBI) field, raising public awareness of the potential long-term effects of mild and moderate repetitive TBI, which has been reco...
Source: Experimental Neurology - June 6, 2015 Category: Neurology Authors: Ojo JO, Mouzon BC, Crawford F Tags: Exp Neurol Source Type: research

Dynamic changes in phrenic motor output following high cervical hemisection in the decerebrate rat.
Abstract Hemisection of the spinal cord at C2 eliminates ipsilateral descending drive to the phrenic nucleus and causes hemidiaphragmatic paralysis in rats. Phrenic nerve (PhN) or diaphragmatic activity ipsilateral to hemisection can occasionally be induced acutely following hemisection by respiratory stressors (i.e., hypercapnia, asphyxia, contralateral phrenicotomy) and becomes spontaneously active days-to-weeks later. These investigations, however, are potentially confounded by the use of anesthesia, which may suppress spontaneously-active crossed phrenic pathways. Experiments were performed on vecuronium-paral...
Source: Experimental Neurology - June 6, 2015 Category: Neurology Authors: Ghali MG Tags: Exp Neurol Source Type: research

Systemic pyruvate administration markedly reduces neuronal death and cognitive impairment in a rat model of Alzheimer's disease.
Abstract Alzheimer's disease (AD) is a major neurodegenerative disease of old age, characterized by progressive cognitive impairment, dementia and atrophy of the central nervous system. Amyloid - β (Aβ) oligomers are derived from proteolytic cleavage of amyliod precursor protein (APP) and recognized as the primary neurotoxic agents in AD. Pyruvate has a protective effect against Aβ oligomer-induced neuronal cell death and inhibition of long-term potentiation (LTP) in hippocampal slice cultures, leading us to investigate the effect of systemic pyruvate administration in an intracerebroventricular A&b...
Source: Experimental Neurology - June 6, 2015 Category: Neurology Authors: Wang X, Hu X, Yang Y, Takata T, Sakurai T Tags: Exp Neurol Source Type: research

Gender- and anxiety level-dependent effects of perinatal stress exposure on medial prefrontal cortex.
In this study, we evaluated the dendritic morphology of medial PFC neurons in rats subjected to perinatal stress exposure. Unbiased stereological counting methods showed that total number estimation of c-Fos (+) nuclei, indicating the neuronal activation upon stressful challenge, significantly increased in high anxious animals compared with low anxious and control groups, in both gender. Golgi-Cox staining of neurons displayed anxiety level- and sex-dependent reduction in the dendritic complexity and spine density of pyramidal neurons, especially in the stressed males. While the total length of dendrites were not correlati...
Source: Experimental Neurology - June 6, 2015 Category: Neurology Authors: Soztutar E, Colak E, Ulupinar E Tags: Exp Neurol Source Type: research

Therapeutic hypothermia for stroke: where to go?
Abstract Ischemic stroke is a major cause of death and long-term disability worldwide. Thrombolysis with recombinant tissue plasminogen activator is the only proven and effective treatment for acute ischemic stroke; however, therapeutic hypothermia is increasingly recognized as having a tissue-protective function and positively influencing neurological outcome, especially in cases of ischemia caused by cardiac arrest or hypoxic-ischemic encephalopathy in newborns. Yet, many aspects of hypothermia as a treatment for ischemic stroke remain unknown. Large-scale studies examining the effects of hypothermia on stroke a...
Source: Experimental Neurology - June 6, 2015 Category: Neurology Authors: Han Z, Liu X, Luo Y, Ji X Tags: Exp Neurol Source Type: research

Interleukin-6 mediates enhanced thrombus development in cerebral arterioles following a brief period of focal brain ischemia.
CONCLUSIONS: The increased vulnerability of the cerebral vasculature to thrombus development after MCAo/R is mediated by IL-6, which is likely derived from brain cells rather than circulating blood cells. These findings suggest that anti-IL-6 therapy may reduce the likelihood of cerebral thrombus development after a transient ischemic attack. PMID: 26054883 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 5, 2015 Category: Neurology Authors: Tang YH, Vital S, Russell J, Seifert H, Neil Granger D Tags: Exp Neurol Source Type: research

Neurotrophin Selectivity in Organizing Topographic Regeneration of Nociceptive Afferents.
This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFR-α3, which only promoted mistargeted regeneration. PMID: 26054884 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 5, 2015 Category: Neurology Authors: Kelamangalath L, Tang X, Bezik K, Sterling N, Son YJ, Smith GM Tags: Exp Neurol Source Type: research