Transferrin and thyroid hormone converge in the control of myelinogenesis.
Abstract Myelination is a concerted mechanism tightly regulated in the brain. Although several factors are known to participate during this process, the complete sequence of events is far from being fully elucidated. Separate effects of apotransferrin (aTf) and thyroid hormone (TH) are well documented on rat myelin formation. TH promotes the maturation of oligodendrocyte progenitors (OPCs) into myelinating oligodendrocytes (OLGs), while aTf is able to induce the commitment of neural stem cells (NSCs) toward the oligodendroglial linage and favors OLG maturation. We have also demonstrated that Tf mRNA exhibited a se...
Source: Experimental Neurology - January 14, 2015 Category: Neurology Authors: Marziali LN, Garcia CI, Pasquini JM Tags: Exp Neurol Source Type: research

Favorable modulation in neurotransmitters: Effects of chronic anterior thalamic nuclei stimulation observed in epileptic monkeys.
This study investigated the changes in the amino acid levels during chronic, single-sided ATN-stimulation in the hippocampi of rhesus monkeys with mesial temporal lobe epilepsy induced by kainic acid (KA). The concentrations of glutamate, γ-aminobutyric acid, aspartate and taurine in the dialysates from bilateral hippocampi were determined at multiple time points using high-performance liquid chromatography. The results showed that after KA administration, the aspartate, γ-aminobutyric acid and taurine levels increased significantly in the sham-stimulation group, although the γ-aminobutyric acid and tauri...
Source: Experimental Neurology - January 14, 2015 Category: Neurology Authors: Shi L, Yang AC, Li JJ, Meng DW, Jiang B, Zhang JG Tags: Exp Neurol Source Type: research

How clinical trials of myasthenia gravis can inform pre-clinical drug development.
Abstract Pre-clinical evaluations often provide the rationale for therapeutic assessments in humans; however, in many diseases an agent found successful in animal models does not show efficacy in human subjects. Our contention is that the approach of rigorous, clinical trials can be used to inform how preclinical assessments should be performed. Clinical trials in humans are carefully designed investigations executed with consideration of critical methodological issues, such as pre-specified entrance criteria and validated, outcome measures coupled with power analysis to identify sample size. Blinding of evaluator...
Source: Experimental Neurology - January 13, 2015 Category: Neurology Authors: Rostedt Punga A, Kaminski HJ, Richman DP, Benatar M Tags: Exp Neurol Source Type: research

Na(+)/H(+) exchanger in the regulation of platelet activation and paradoxical effects of cariporide.
Abstract Platelets are anucleated cell fragments derived from mature megakaryocytes and function in hemostasis when the endothelium is injured. Hemostasis involving platelets can be divided into four phases: adhesion, activation, secretion, and aggregation. Platelet activation requires a rise in intracellular Ca(2+) concentrations and results in both a morphological change and the secretion of platelet granule contents. Na(+)/H(+) exchanger isoform 1 (NHE1) regulates the intracellular pH (pHi) and the volume of platelets. In addition, NHE1 plays a large role in platelet activation. Thrombus generation involves NHE...
Source: Experimental Neurology - January 13, 2015 Category: Neurology Authors: Chang HB, Gao X, Nepomuceno R, Hu S, Sun D Tags: Exp Neurol Source Type: research

Aquaporin-1 water permeability as a novel determinant of axonal regeneration in dorsal root ganglion neurons.
Abstract Dorsal root ganglion (DRG) neurons transduce peripheral pain signals through small-diameter, non-myelinated C-fibers, which, when injured, can regenerate to restore pain sensation. Water channel aquaporin-1 (AQP1) is expressed at the plasma membrane of cell bodies and axons of DRG neurons, where it modulates the sensing of certain types of pain. Here, we found that AQP1 is also involved in DRG axonal growth and regeneration by a mechanism that may involve water transport-facilitated extension of axonal outgrowths. Spontaneous and nerve growth factor-stimulated axonal extension was reduced in cultures of A...
Source: Experimental Neurology - January 10, 2015 Category: Neurology Authors: Zhang H, Verkman AS Tags: Exp Neurol Source Type: research

Targeting the sigma-1 receptor chaperone in the treatment of perinatal brain injury.
This study suggests that sigma-1 receptor agonists could be potential preventive and therapeutic drugs for perinatal brain injury, although a pharmacological experiment using a sigma-1 receptor antagonist was not performed. This commentary aims to highlights the key findings of this article in a broader context, emphasizing the future potential therapeutic applications in patients with perinatal brain injury. PMID: 25585013 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 10, 2015 Category: Neurology Authors: Hashimoto K Tags: Exp Neurol Source Type: research

G-CSF Attenuates Neuroinflammation and Stabilizes the Blood-Brain Barrier via the PI3K/Akt/GSK-3β Signaling Pathway Following Neonatal Hypoxia-Ischemia in Rats.
CONCLUSIONS:: We demonstrate G-CSF plays a pivotal role in attenuating neuroinflammation and BBB disruption following HI by inactivating GSK-3β through the PI3K/Akt pathway. PMID: 25585014 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 10, 2015 Category: Neurology Authors: Li L, McBride DW, Doycheva D, Dixon BJ, Krafft PR, Zhang JH, Tang J Tags: Exp Neurol Source Type: research

Mitochondria-associated microRNAs in rat hippocampus following traumatic brain injury.
Abstract Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI, however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediator...
Source: Experimental Neurology - January 3, 2015 Category: Neurology Authors: Wang W, Visavadiya NP, Pandya JD, Nelson PT, Sullivan PG, Springer JE Tags: Exp Neurol Source Type: research

The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model.
KV Abstract Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions, and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesi...
Source: Experimental Neurology - December 24, 2014 Category: Neurology Authors: Geis C, Ritter C, Ruschil C, Weishaupt A, Grünewald B, Stoll G, Holmoy T, Misu T, Fujihara K, Hemmer B, Stadelmann C, Bennett JL, Sommer C, Toyka KV Tags: Exp Neurol Source Type: research

Differential subcellular Ca(2+) signaling in a highly specialized subpopulation of astrocytes.
Abstract Recent evidence suggests that astrocytes do not serve a mere buffering function, but exhibit complex signaling pathways, disturbance of which contributes significantly to the pathophysiology of CNS diseases. Little is known regarding the intracellular signaling pathways in specialized optic nerve head astrocytes (ONHAs), the major glia cell type in non-myelinated optic nerve head. Here we show the differential subcellular expression of intracellular Ca(2+) channels in ONHAs. Expression of type 1 and type 3 inositol-1-4-5,-trisphosphate receptors (IP3Rs) in the endoplasmic reticulum and type 2 IP3Rs the nu...
Source: Experimental Neurology - December 24, 2014 Category: Neurology Authors: Kaja S, Payne AJ, Patel KR, Naumchuk Y, Koulen P Tags: Exp Neurol Source Type: research

Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis.
Abstract Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endpl...
Source: Experimental Neurology - December 24, 2014 Category: Neurology Authors: Phillips WD, Christadoss P, Losen M, Punga A, Shigemoto K, Verschuuren J, Vincent A Tags: Exp Neurol Source Type: research

Voltage-gated Ca(++) entry promotes oligodendrocyte progenitor cells maturation and myelination in vitro.
ez PM Abstract We have previously shown that the expression of voltage-operated Ca(++) channels (VOCCs) is highly regulated in the oligodendroglial lineage and is essential for proper oligodendrocyte progenitor cells (OPCs) migration. Here we assessed the role of VOCCs, in particular the L-type, in oligodendrocyte maturation. We used pharmacological treatments to activate or block voltage-gated Ca(++) uptake and siRNAs to specifically knockdown the L-type VOCC in primary cultures of mouse OPCs. Activation of VOCCs by plasma membrane depolarization increased OPC morphological differentiation as well as the expressi...
Source: Experimental Neurology - December 24, 2014 Category: Neurology Authors: Cheli VT, Santiago González DA, Spreuer V, Paez PM Tags: Exp Neurol Source Type: research

Activation of either the ETA or the ETB receptors is involved in the development of electrographic seizures followed intrahippocampal infusion of the endothelin-1 in immature rats.
, Kubová H Abstract The period around birth is a risky time for stroke in infants, which is associated with two major acute and subacute processes: anatomical damage and seizures. It is unclear to what extent each of these processes independently contributes to poor outcome. Furthermore, it is unclear whether there is an interaction between the two processes - does seizure activity cause additional brain damage beyond that produced by ischemia and/or does brain damage foster seizures? The model of focal cerebral ischemia induced by the intrahippocampal infusion of the endothelin-1 (ET-1) in 12-day-old rat w...
Source: Experimental Neurology - December 24, 2014 Category: Neurology Authors: Tsenov G, Vondraková K, Otáhal J, Burchfiel J, Kubová H Tags: Exp Neurol Source Type: research

Hyperbaric Oxygen Preconditioning Attenuates Hemorrhagic Transformation through Increasing PPARγ in Hyperglycemic MCAO Rats.
Hyperbaric Oxygen Preconditioning Attenuates Hemorrhagic Transformation through Increasing PPARγ in Hyperglycemic MCAO Rats. Exp Neurol. 2014 Dec 23; Authors: Bian H, Hu Q, Liang X, Chen D, Li B, Tang J, Zhang JH Abstract Hyperbaric oxygen preconditioning (HBO-PC) has been demonstrated to attenuate hemorrhagic transformation (HT) after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. However, the mechanisms remain to be illustrated. Recently, HBO-PC has been shown to activate peroxisome proliferator-activated receptor-gamma (PPARγ) by increasing 15d-PGJ2 in primary cultured n...
Source: Experimental Neurology - December 23, 2014 Category: Neurology Authors: Bian H, Hu Q, Liang X, Chen D, Li B, Tang J, Zhang JH Tags: Exp Neurol Source Type: research

A novel and robust conditioning lesion induced by ethidium bromide.
This study provides a new method for investigating the underlying mechanisms of the conditioning response and suggests that loss of the peripheral myelin may be a major signal to change the intrinsic growth state of adult sensory neurons and promote regeneration. PMID: 25541322 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - December 22, 2014 Category: Neurology Authors: Hollis ER, Ishiko N, Tolentino K, Doherty E, Rodriguez MJ, Calcutt NA, Zou Y Tags: Exp Neurol Source Type: research

Human glial progenitor engraftment and gene expression is independent of the ALS environment.
Abstract Although Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, basic research studies have highlighted that astrocytes contribute to the disease process. Therefore, strategies which replace the diseased astrocyte population with healthy astrocytes may protect against motor neuron degeneration. Our studies have sought to evaluate astrocyte replacement using glial-restricted progenitors (GRPs), which are lineage-restricted precursors capable of differentiating into astrocytes after transplantation. The goal of our current study was to evaluate how transplantation to the diseased ALS spinal cord ver...
Source: Experimental Neurology - December 16, 2014 Category: Neurology Authors: Haidet-Phillips AM, Doreswamy A, Gross SK, Tang X, Campanelli JT, Maragakis NJ Tags: Exp Neurol Source Type: research

Optimized methods for epilepsy therapy development using an etiologically realistic model of focal epilepsy in the rat.
Abstract Conventionally developed antiseizure drugs fail to control epileptic seizures in about 30% of patients, and no treatment prevents epilepsy. New etiologically realistic, syndrome-specific epilepsy models are expected to identify better treatments by capturing currently unknown ictogenic and epileptogenic mechanisms that operate in the corresponding patient populations. Additionally, the use of electrocorticography permits better monitoring of epileptogenesis and the full spectrum of acquired seizures, including focal nonconvulsive seizures that are typically difficult to treat in humans. Thus, the combined...
Source: Experimental Neurology - December 16, 2014 Category: Neurology Authors: Eastman CL, Fender JS, Temkin NR, D'Ambrosio R Tags: Exp Neurol Source Type: research

Neurochemical excitation of thoracic propriospinal neurons improves hindlimb stepping in adult rats with spinal cord lesions.
Abstract Using an in vitro neonatal rat brainstem-spinal cord preparation, we previously showed that cervicothoracic propriospinal neurons contribute to descending transmission of the bulbospinal locomotor command signal, and neurochemical excitation of these neurons facilitates signal propagation. The present study examined the relevance of these observations to adult rats in vivo. The first aim was to determine the extent to which rats are able to spontaneously recover hindlimb locomotor function in the presence of staggered contralateral hemisections (left T2-4 and right T9-11) designed to abolish all long dire...
Source: Experimental Neurology - December 16, 2014 Category: Neurology Authors: Cowley KC, MacNeil BJ, Chopek JW, Sutherland S, Schmidt BJ Tags: Exp Neurol Source Type: research

Involvement of platelet-derived growth factor receptor β in fibrosis through extracellular matrix protein production after ischemic stroke.
In conclusion, the expression level of PDGFRβ may be a crucial determinant of fibrosis after ischemic stroke. Moreover, PDGFRβ signaling participates in the production of fibronectin and collagen type I after ischemic stroke. PMID: 25510317 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - December 12, 2014 Category: Neurology Authors: Makihara N, Arimura K, Ago T, Tachibana M, Nishimura A, Nakamura K, Matsuo R, Wakisaka Y, Kuroda J, Sugimori H, Kamouchi M, Kitazono T Tags: Exp Neurol Source Type: research

Biphasic bisperoxovanadium administration and Schwann cell transplantation for repair after cervical contusive spinal cord injury.
Abstract Schwann cells (SCs) hold promise for spinal cord injury (SCI) repair; however, there are limitations for use as a lone treatment. We showed acute inhibition of the phosphatase and tensin homologue (PTEN) by bisperoxovanadium (bpV) was neuroprotective and enhanced function following cervical hemicontusion SCI. We hypothesized that combining acute bpV therapy and delayed SC engraftment would further improve neuroprotection and recovery after cervical SCI. Adult female Sprague Dawley (SD) rats were randomly sorted into 5 groups: sham, vehicle, bpV, SC transplantation, and bpV+SC transplantation. SCs were iso...
Source: Experimental Neurology - December 12, 2014 Category: Neurology Authors: Walker CL, Wang X, Bullis C, Liu NK, Lu Q, Fry C, Deng L, Xu XM Tags: Exp Neurol Source Type: research

Early hyperactivity in lateral entorhinal cortex is associated with elevated levels of AβPP metabolites in the Tg2576 mouse model of Alzheimer's disease.
Early hyperactivity in lateral entorhinal cortex is associated with elevated levels of AβPP metabolites in the Tg2576 mouse model of Alzheimer's disease. Exp Neurol. 2014 Dec 11; Authors: Xu W, Fitzgerald S, Nixon RA, Levy E, Wilson DA Abstract Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly today. One of the earliest symptoms of AD is olfactory dysfunction. The present study investigated the effects of amyloid β precursor protein (AβPP) metabolites, including amyloid-β (Aβ) and AβPP C-terminal fragments (C...
Source: Experimental Neurology - December 11, 2014 Category: Neurology Authors: Xu W, Fitzgerald S, Nixon RA, Levy E, Wilson DA Tags: Exp Neurol Source Type: research

Desmoplakin is involved in organization of an adhesion complex in peripheral nerve regeneration after injury.
In this study, we analyzed the expression and function of desmoplakin in peripheral nerve regeneration. Desmoplakin was upregulated in spinal cord motoneurons after sciatic nerve injury. Conditional ablation of desmoplakin in motoneurons demonstrated that desmoplakin is necessary for normal motor regeneration. SiRNA and desmoplakin deletion-constructs revealed a role of desmoplakin in neurite extension in vitro. A complex of N-cadherin, plakoglobin, desmoplakin and vimentin was shown in motoneuronal cell cultures and peripheral nerves after injury in vivo. Motor nerve fiber regeneration and localization of N-cadherin and v...
Source: Experimental Neurology - December 10, 2014 Category: Neurology Authors: Gess B, Röhr D, Lange E, Halfter H, Young P Tags: Exp Neurol Source Type: research

GDNF preconditioning can overcome Schwann cell phenotypic memory.
Abstract While it is known that Schwann cells (SCs) provide cues to enhance regeneration following peripheral nerve injury, the effect of SC phenotypic memory (muscle or cutaneous nerve-derived) on enhancing axonal regeneration and functional recovery has been unclear in the literature. In particular, differences between muscle and cutaneous nerve-derived SC may encourage specific motor or sensory axonal guidance in cell/tissue transplantation therapies. Thus, the goal of this study was to determine whether phenotypically matched combinations of neurons and SCs stimulate greater axonal extension compared to mismat...
Source: Experimental Neurology - December 10, 2014 Category: Neurology Authors: Marquardt LM, Sakiyama-Elbert SE Tags: Exp Neurol Source Type: research

Spreading depression transiently disrupts myelin via interferon-gamma signaling.
Abstract Multiple sclerosis and migraine with aura are clinically correlated and both show imaging changes suggestive of myelin disruption. Furthermore, cortical myelin loss in the cuprizone animal model of multiple sclerosis enhances susceptibility to spreading depression, the likely underlying cause of migraine with aura. Since multiple sclerosis pathology involves inflammatory T cell lymphocyte production of interferon-gamma and a resulting increase in oxidative stress, we tested the hypothesis that spreading depression disrupts myelin through similar signaling pathways. Rat hippocampal slice cultures were init...
Source: Experimental Neurology - December 8, 2014 Category: Neurology Authors: Pusic AD, Mitchell HM, Kunkler PE, Klauer N, Kraig RP Tags: Exp Neurol Source Type: research

Environmental enrichment: Evidence for an unexpected therapeutic influence.
Abstract Environmental enrichment produces wide-ranging effects in the brain at molecular, cellular, network, and behavioral levels. The changes in neuronal plasticity are driven by changes in neurotransmitters, neurotrophic factors, neuronal morphology, neurogenesis, network properties of the brain, and behavioral correlates of learning and memory. Exposure to an enriched environment has also demonstrated intriguing possibilities for treatment of a variety of neurodegenerative diseases including Huntington's disease, Alzheimer's disease, and Parkinson's disease. The effect of environmental enrichment in epilepsy,...
Source: Experimental Neurology - December 4, 2014 Category: Neurology Authors: Kotloski RJ, Sutula TP Tags: Exp Neurol Source Type: research

Neural Progenitor Cell Transplantation Promotes Neuroprotection, Enhances Hippocampal Neurogenesis, and Improves Cognitive Outcomes after Traumatic Brain Injury.
In this study, we hypothesized that pericontusional transplantation of NPCs genetically modified to secrete a synthetic, human multineurotrophin (MNTS1) would overcome some of the limitations of traditional neurotrophin therapy. MNTS1 is a multifunctional neurotrophin that binds all three tropomyosin-related kinase (Trk) receptors, recapitulating the prosurvival activity of 3 endogenous mature neurotrophins. NPCs obtained from rat fetuses at E15 were transduced with lentiviral vectors containing MNTS1 and GFP constructs (MNTS1-NPCs) or fluorescent constructs alone (control GFP-NPCs). Adult rats received fluid percussion-in...
Source: Experimental Neurology - December 4, 2014 Category: Neurology Authors: Blaya MO, Tsoulfas P, Bramlett HM, Dalton Dietrich W Tags: Exp Neurol Source Type: research

Thrombospondin-4 and Excitatory Synaptogenesis Promote Spinal Sensitization after Painful Mechanical Joint Injury.
This study investigates the role of TSP4 in the development and maintenance of persistent pain following injurious facet joint distraction in rats and tests the hypothesis that excitatory synaptogenesis contributes to such pain. Painful facet joint loading induces dorsal horn excitatory synaptogenesis along with decreased TSP4 in the DRG and increased astrocytic release of TSP4 in the spinal cord, all of which parallel the time course of sustained tactile allodynia. Blocking injury-induced spinal TSP4 expression with antisense oligonucleotides or reducing TSP4 activity at its neuronal receptor in the spinal cord with gabap...
Source: Experimental Neurology - December 4, 2014 Category: Neurology Authors: Crosby ND, Zaucke F, Kras JV, Dong L, Luo ZD, Winkelstein BA Tags: Exp Neurol Source Type: research

Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology.
Abstract Alzheimer's disease is the most prevalent tauopathy and cause of dementia. We investigate the hypothesis that reactivation of plasticity can restore function in the presence of neuronal damage resulting from tauopathy. We investigated two models with tau hyperphosphorylation, aggregation and neurodegeneration: a transgenic mouse model in which the mutant P301S tau is expressed in neurons (Tg P301S), and a model in which an adeno-associated virus expressing P301S tau (AAV-P301S) was injected in perirhinal cortex, a region critical for object recognition (OR) memory. Both models show profound loss of OR mem...
Source: Experimental Neurology - December 4, 2014 Category: Neurology Authors: Yang S, Cacquevel M, Saksida LM, Bussey TJ, Schneider BL, Aebischer P, Melani R, Pizzorusso T, Fawcett JW, Spillantini MG Tags: Exp Neurol Source Type: research

Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination.
Abstract Very Low Birth Weight (VLBW) premature infants experience numerous, often self-limited non-bradycardic episodes of intermittent hypoxemia (IH). We hypothesized that these episodes of IH affect postnatal white matter (WM) development causing hypomyelination and neurological handicap in the absence of cellular degeneration. Based on clinical data from ten VLBW neonates; a severity, daily duration and frequency of non-bradycardic IH episodes were reproduced in neonatal mice. Changes in heart rate and cerebral blood flow during IH were recorded. A short-term and long-term neurofunctional performance, cerebral...
Source: Experimental Neurology - December 1, 2014 Category: Neurology Authors: Juliano C, Sosunov S, Niatsetskaya Z, Isler JA, Utkina-Sosunova I, Jang I, Ratner V, Ten V Tags: Exp Neurol Source Type: research

Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections.
Abstract Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, paralysis and death by ventilatory failure. In rodent ALS models: 1) breathing capacity is preserved until late in disease progression despite major respiratory motor neuron death, suggesting unknown forms of compensatory respiratory plasticity; and 2) spinal microglia become activated in association with motor neuron cell death. Here, we report a novel experimental model to study the impact of respiratory motor neuron death on compensatory responses without many complications attendant to spontaneous motor neuron disease. I...
Source: Experimental Neurology - December 1, 2014 Category: Neurology Authors: Nichols NL, Vinit S, Bauernschmidt L, Mitchell GS Tags: Exp Neurol Source Type: research

Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid.
Abstract Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice wit...
Source: Experimental Neurology - December 1, 2014 Category: Neurology Authors: Iyengar SS, LaFrancois JJ, Friedman D, Drew LJ, Denny CA, Burghardt NS, Wu MV, Hsieh J, Hen R, Scharfman HE Tags: Exp Neurol Source Type: research

Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia.
Abstract MiR-181 has deleterious effects on stroke outcome, and reducing miR-181a levels prior to middle cerebral artery occlusion (MCAO) was shown previously to be protective. Here we tested the effect of post-ischemic treatment with miR-181a antagomir by intracerebroventricular and intravenous routes of administration on infarct size, neurological outcome, inflammatory response and long term behavioral outcome. Post-treatment with miR-181a antagomir significantly reduced infarction size, improved neurological deficits and reduced NF-κB activation, numbers of infiltrating leukocytes and levels of Ibal. Targ...
Source: Experimental Neurology - November 26, 2014 Category: Neurology Authors: Xu LJ, Ouyang YB, Xiong X, Stary CM, Giffard RG Tags: Exp Neurol Source Type: research

Nrf2-ARE Activator Carnosic Acid Decreases Mitochondrial Dysfunction, Oxidative Damage and Neuronal Cytoskeletal Degradation Following Traumatic Brain Injury in Mice.
This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI. PMID: 25432068 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - November 25, 2014 Category: Neurology Authors: Miller DM, Singh IN, Wang JA, Hall ED Tags: Exp Neurol Source Type: research

Neuroepigenetics: Introduction to the special issue on epigenetics in neurodevelopment and neurological diseases.
PMID: 25432069 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - November 25, 2014 Category: Neurology Authors: Ming GL Tags: Exp Neurol Source Type: research

Application of neurophysiological biomarkers for Huntington's disease: Evaluating a phosphodiesterase 9A inhibitor.
e;s M Abstract Several neurophysiological abnormalities have been described in Huntington's disease, including auditory gating deficit, which are considered to reflect impaired brain information-processing. Since transgenic animal models of Huntington's disease capture basic neuropathology of the disorder, auditory gating was studied in BACHD (line5) transgenic rats and Q175 transgenic mice, together with local field gamma power in the hippocampus and primary auditory cortex. Using clinically equivalent acoustic-stimulation paradigms, impaired auditory gating was detected in transgenic BACHD rats under anesthesia ...
Source: Experimental Neurology - October 11, 2014 Category: Neurology Authors: Nagy D, Tingley FD, Stoiljkovic M, Hajós M Tags: Exp Neurol Source Type: research

The anti-inflammatory peptide stearyl-norleucine-VIP delays disease onset and extends survival in a rat model of inherited amyotrophic lateral sclerosis.
s E Abstract Vasoactive intestinal peptide (VIP) has potent immune modulatory actions that may influence the course of neurodegenerative disorders associated with chronic inflammation. Here, we show the therapeutic benefits of a modified peptide agonist stearyl-norleucine-VIP (SNV) in a transgenic rat model of amyotrophic lateral sclerosis (mutated superoxide dismutase 1, hSOD1(G93A)). When administered by systemic every-other-day intraperitoneal injections during a period of 80days before disease, SNV delayed the onset of motor dysfunction by no less than three weeks, while survival was extended by nearly two mon...
Source: Experimental Neurology - October 10, 2014 Category: Neurology Authors: Goursaud S, Schäfer S, Dumont AO, Vergouts M, Gallo A, Desmet N, Deumens R, Hermans E Tags: Exp Neurol Source Type: research

Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease.
Abstract The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess...
Source: Experimental Neurology - October 5, 2014 Category: Neurology Authors: Bradbury AM, Gray-Edwards HL, Shirley JL, McCurdy VJ, Colaco AN, Randle AN, Christopherson PW, Bird AC, Johnson AK, Wilson DU, Hudson JA, De Pompa NL, Sorjonen DC, Brunson BL, Jeyakumar M, Platt FM, Baker HJ, Cox NR, Sena-Esteves M, Martin DR Tags: Exp Neurol Source Type: research

Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP(+) toxicity.
Abstract Exercise induces oxidative stress, which may activate adaptive antioxidant responses. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the defense of oxidative stress by regulating the expression of antioxidant enzymes, gamma-glutamylcysteine ligase (γGCL) and heme oxygenase-1 (HO-1). We investigated whether treadmill exercise protects dopaminergic neurons by regulating the Nrf2 antioxidant system in a 1-methyl-4-phenylpyridine (MPP(+))-induced parkinsonian rat model. We found that MPP(+) induced early decreases in total glutathione level and Nrf2/γGCLC (catalytic ...
Source: Experimental Neurology - October 5, 2014 Category: Neurology Authors: Tsou YH, Shih CT, Ching CH, Huang JY, Jen CJ, Yu L, Kuo YM, Wu FS, Chuang JI Tags: Exp Neurol Source Type: research

Early life seizures: Evidence for chronic deficits linked to autism and intellectual disability across species and models.
Abstract Recent work in Exp Neurol by Lugo et al. (2014b) demonstrated chronic alterations in sociability, learning and memory following multiple early life seizures (ELSs) in a mouse model. This work adds to the growing body of evidence supporting the detrimental nature of ELSs on the developing brain to contribute to aspects of an autistic phenotype with intellectual disability. Review of the face validity of behavioral testing and the construct validity of the models used informs the predictive ability and thus the utility of these models to translate underlying molecular and cellular mechanisms into future hum...
Source: Experimental Neurology - October 2, 2014 Category: Neurology Authors: Bernard PB, Benke TA Tags: Exp Neurol Source Type: research

NF-κB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke.
NF-κB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke. Exp Neurol. 2014 Sep 30; Authors: Cui L, Duchamp NS, Boston DJ, Ren X, Zhang X, Hu H, Zhao LR Abstract Chronic stroke is the phase of brain recovery and repair generally beginning 3 months after stroke onset. No pharmaceutical approach is currently available to enhance brain repair in the chronic stroke. We have previously determined the therapeutic effects of stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) alone or in combination (SCF+G-CSF) in an animal mo...
Source: Experimental Neurology - September 30, 2014 Category: Neurology Authors: Cui L, Duchamp NS, Boston DJ, Ren X, Zhang X, Hu H, Zhao LR Tags: Exp Neurol Source Type: research

Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats.
Abstract Previously, we showed that activation of the spinal CXCL9, 10/CXCR3 pathway mediated bone cancer pain (BCP) in rats. However, the cellular mechanism involved is poorly understood. Here, we found that the activated CXCR3 was co-localized with either neurons, microglia, and astrocytes in the spinal cord, or non-peptidergic-, peptidergic-, and A-type neurons in the dorsal root ganglion. The inoculation of Walker-256 mammary gland carcinoma cells into the rat's tibia induced a time-dependent phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2) in the spinal cord, and CXCR3 was necessary f...
Source: Experimental Neurology - September 30, 2014 Category: Neurology Authors: Guan XH, Fu QC, Shi D, Bu HL, Song ZP, Xiong BR, Shu B, Xiang HB, Xu B, Manyande A, Cao F, Tian YK Tags: Exp Neurol Source Type: research

Electric Signals Regulate Directional Migration of Ventral Midbrain Derived Dopaminergic Neural Progenitor Cells via Wnt / GSK3β signaling.
Electric Signals Regulate Directional Migration of Ventral Midbrain Derived Dopaminergic Neural Progenitor Cells via Wnt / GSK3β signaling. Exp Neurol. 2014 Sep 26; Authors: Liu J, Zhu B, Zhang G, Wang J, Tian W, Ju G, Wei X, Song B Abstract Neural progenitor cell (NPC) replacement therapy is a promising treatment for neurodegenerative disorders including Parkinson's disease (PD). It requires a controlled directional migration and integration of NPCs, for example dopaminergic (DA) progenitor cells, into the damaged host brain tissue. There is, however, only limited understanding of how to regulat...
Source: Experimental Neurology - September 26, 2014 Category: Neurology Authors: Liu J, Zhu B, Zhang G, Wang J, Tian W, Ju G, Wei X, Song B Tags: Exp Neurol Source Type: research

Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism.
In this study, we investigated the neuroprotective mechanism and therapeutic effect of ALDH2 in rotenone models for parkinsonism. Overexpression of wild-type ALDH2 gene, but not the enzymatically deficient mutant ALDH2*2 (E504K), reduced rotenone-induced cell death. Application of a potent activator of ALDH2, Alda-1, was effective in protecting against rotenone-induced apoptotic cell death in both SH-SY5Y cells and primary cultured substantia nigra (SN) dopaminergic neurons. In addition, intraperitoneal administration of Alda-1 significantly reduced rotenone- or MPTP-induced death of SN tyrosine hydroxylase (TH)-positive d...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, Huang YC, Chen YJ, Chen CL, Chang YM, Wang HL, Lu CS Tags: Exp Neurol Source Type: research

Epigenetic Mechanisms of Neuroplasciticy and the Implications for Stroke Recovery.
Abstract Ischemic stroke is a devastating brain injury and an important cause of neurologic disability worldwide and across the lifespan. Despite the physical, social, and economic burdens of this disease there is only a single approved medicine for the treatment of acute stroke, and its use is unfortunately limited to the small fraction of patients presenting within the narrow therapeutic window. Following stroke, there is a period of plasticity involving cell genesis, axon growth, and synaptic modulation that is essential to spontaneous recovery. Treatments focusing on neuroprotection and enhancing recovery have...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Felling RJ, Song H Tags: Exp Neurol Source Type: research

Postnatal glucocorticoid-induced hypomyelination, gliosis, neurologic deficits are dose-dependent, preparation-specific, and reversible.
Abstract Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear. We hypothesized that postnatal GC would induce hypomyelination and motor impairment in a preparation- and dose-specific manner, and that GC receptor (GR) inhibition might restore myelination and neurolo...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Zia MT, Vinukonda G, Vose L, Bhimavarapu BB, Iacobas S, Pandey NK, Beall AM, Dohare P, LaGamma EF, Iacobas DA, Ballabh P Tags: Exp Neurol Source Type: research

Behavioral effects and mechanisms of migraine pathogenesis following estradiol exposure in a multibehavioral model of migraine in rat.
Abstract Migraine is one of the most common neurological disorders, leading to more than 1% of total disability reported and over 68 million visits to emergency rooms or physician's offices each year in the United States. Three times as many women as men have migraine, and while the mechanism behind this is not well understood, 17β-estradiol (estradiol) has been implicated to play a role. Studies have demonstrated that exposure to estrogen can lead to activation of inflammatory pathways, changes in sodium gated channel activity, as well as enhanced vasodilation and allodynia. Estradiol receptors are found in ...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Vermeer LM, Gregory E, Winter MK, McCarson KE, Berman NE Tags: Exp Neurol Source Type: research

The α7 nicotinic receptor agonist ABT-107 protects against nigrostriatal damage in rats with unilateral 6-hydroxydopamine lesions.
The objective of this study was twofold: first, to test the protective potential of ABT-107, an agonist with high selectivity for α7 nAChRs; and second, to investigate its cellular mechanism of action. Rats were implanted with minipumps containing ABT-107 (0.25mg/kg/d). In addition, we tested the effect of nicotine (1mg/kg/d) as a positive control, and also DMXB (2mg/kg/d) which acts primarily with α7 but also α4β2* nAChRs. Two wk after minipump placement, the rats were lesioned by unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Lesioning alone decreased cont...
Source: Experimental Neurology - September 24, 2014 Category: Neurology Authors: Bordia T, McGregor M, Papke RL, Decker MW, Michael McIntosh J, Quik M Tags: Exp Neurol Source Type: research

Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves.
Abstract The small GTPase RhoA and its down-stream effector Rho-kinase (ROCK) are important effector molecules of the neuronal cytoskeleton. Modulation of the RhoA/ROCK pathway has been shown to promote axonal regeneration, however in vitro and animal studies are inconsistent regarding the extent of axonal outgrowth induced by pharmacological inhibition of ROCK. We hypothesized that injury to sensory and motor nerves result in diverse activation levels of RhoA, which may impact the response of those nerve fiber modalities to ROCK inhibition. We therefore examined the effects of Y-27632, a chemical ROCK inhibitor, ...
Source: Experimental Neurology - September 24, 2014 Category: Neurology Authors: Joshi AR, Bobylev I, Zhang G, Sheikh K, Lehmann HC Tags: Exp Neurol Source Type: research

Combination of Methamphetamine and HIV-1 gp120 causes distinct long-term alterations of behavior, gene expression, and injury in the central nervous system.
In conclusion, both HIV-1/gp120 and METH caused lasting behavioral impairment in association with neuropathology and altered gene expression. However, combined METH exposure and HIV-1/gp120 expression resulted in the most pronounced, long lasting pre- and post-synaptic alterations coinciding with impaired learning and memory. PMID: 25246228 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 19, 2014 Category: Neurology Authors: Hoefer MM, Sanchez AB, Maung R, de Rozieres CM, Catalan IC, Dowling CC, Thaney VE, Piña-Crespo J, Zhang D, Roberts AJ, Kaul M Tags: Exp Neurol Source Type: research

The influence of the HPG axis on stress response and depressive-like behaviour in a transgenic mouse model of Huntington's disease.
Abstract Huntington's disease (HD) is an autosomal dominant, neurodegenerative disease caused by a CAG tandem repeat mutation encoding a polyglutamine tract expansion in the huntingtin protein. Depression is among the most common affective symptoms in HD but the pathophysiology is unclear. We have previously discovered sexually dimorphic depressive-like behaviours in the R6/1 transgenic mouse model of HD at a pre-motor symptomatic age. Interestingly, only female R6/1 mice display this phenotype. Sexual dimorphism has not been explored in the human HD population despite the well-established knowledge that the clini...
Source: Experimental Neurology - September 19, 2014 Category: Neurology Authors: Du X, Pang TY, Mo C, Renoir T, Wright D, Hannan AJ Tags: Exp Neurol Source Type: research