Fingolimod induces the transition to a nerve regeneration promoting Schwann cell phenotype.
y P Abstract Successful regeneration of injured peripheral nerves is mainly attributed to the plastic behaviour of Schwann cells. Upon loss of axons, these cells trans-differentiate into regeneration promoting repair cells which provide trophic support to regrowing axons. Among others, activation of cJun was revealed to be involved in this process, initiating the stereotypic pattern of Schwann cell phenotype alterations during Wallerian degeneration. Nevertheless, the ability of Schwann cells to adapt and therefore the nerve's potential to regenerate can be limited in particular after long term denervation or in n...
Source: Experimental Neurology - May 6, 2015 Category: Neurology Authors: Heinen A, Beyer F, Tzekova N, Hartung HP, Küry P Tags: Exp Neurol Source Type: research

A Novel Closed-Body Model of Spinal Cord Injury Caused by High-Pressure Air Blasts Produces Extensive Axonal Injury and Motor Impairments.
Abstract Diffuse axonal injury is thought to be the basis of the functional impairments stemming from mild traumatic brain injury. To examine how axons are damaged by traumatic events, such as motor vehicle accidents, falls, sports activities, or explosive blasts, we have taken advantage of the spinal cord with its extensive white matter tracts. We developed a closed-body model of spinal cord injury in mice whereby high-pressure air blasts targeted to lower thoracic vertebral levels produce tensile, compressive, and shear forces within the parenchyma of the spinal cord and thereby cause extensive axonal injury. Ma...
Source: Experimental Neurology - May 6, 2015 Category: Neurology Authors: Del Mar N, von Buttlar X, Yu AS, Guley NH, Reiner A, Honig MG Tags: Exp Neurol Source Type: research

In vivo protein targets for increased quinoprotein adduct formation in aged substantia nigra.
Abstract The selective vulnerability of dopaminergic neurons in the substantia nigra pars compacta in Parkinson's disease, a late age onset neurodegenerative disorder, indicates the involvement of dopamine metabolism in the pathogenesis. Dopamine oxidation produces dopamine o-quinone, which covalently modifies cysteinyl proteins forming quinoprotein adduct. Although quinoprotein formation correlates with increased dopaminergic neurotoxicity, the in vivo protein targets for quinone modification remain unclear. Using two-dimensional gel electrophoresis and nitroblue tetrazolium/glycinate redox-cycling staining, we c...
Source: Experimental Neurology - May 5, 2015 Category: Neurology Authors: Yu G, Liu H, Zhou W, Zhu X, Yu C, Wang N, Zhang Y, Ma J, Zhao Y, Xu Y, Liao L, Ji H, Yuan C, Ma J Tags: Exp Neurol Source Type: research

Neonatal Sensory Nerve Injury-Induced Synaptic Plasticity In The Trigeminal Principal Sensory Nucleus.
Abstract Sensory deprivation studies in neonatal mammals, such as monocular eye closure, whisker trimming, chemical blockade of the olfactory epithelium have revealed the importance of sensory inputs in brain wiring during distinct critical periods. But very few studies have paid attention to the effects of neonatal peripheral sensory nerve damage on synaptic wiring of the central nervous system (CNS) circuits. Peripheral somatosensory nerves differ from other special sensory afferents in that they are more prone to crush or severance because of their locations in the body. Unlike the visual and auditory afferents...
Source: Experimental Neurology - May 5, 2015 Category: Neurology Authors: Lo FS, Erzurumlu RS Tags: Exp Neurol Source Type: research

Enzyme replacement therapy of a novel humanized mouse model of globoid cell leukodystrophy.
Abstract An inherited deficiency of β-galactosylceramidase (GALC) causes the lysosomal storage disease globoid cell leukodystrophy (GLD). The disease is characterized by the accumulation of the cytotoxic metabolite psychosine (galactosylsphingosine), causing rapid degeneration of myelinating cells. Most patients suffer from the infantile form of GLD with onset of disease between 3 and 6 months after birth and death by 2 years of age. The most widely used animal model of GLD, the twitcher mouse, presents with an even more rapid course of disease and death around 40 days of age. We have generated a novel "...
Source: Experimental Neurology - May 5, 2015 Category: Neurology Authors: Matthes F, Andersson C, Stein A, Eistrup C, Fogh J, Gieselmann V, Wenger DA, Matzner U Tags: Exp Neurol Source Type: research

Modeling early-onset post-ischemic seizures in aging mice.
Abstract Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16-20 month-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined...
Source: Experimental Neurology - May 2, 2015 Category: Neurology Authors: Wu C, Wang J, Peng J, Patel N, Huang Y, Gao X, Aljarallah S, Eubanks JH, McDonald R, Zhang L Tags: Exp Neurol Source Type: research

T2 relaxation time post febrile status epilepticus predicts cognitive outcome.
Abstract Evidence from animal models and patient data indicate that febrile status epilepticus (FSE) in early development can result in permanently diminished cognitive abilities. To understand the variability in cognitive outcome following FSE, we used MRI to measure dynamic brain metabolic responses to the induction of FSE in juvenile rats. We then compared these measurements to the ability to learn an active avoidance spatial task weeks later. T2 relaxation times were significantly lower in FSE rats that were task learners in comparison to FSE non-learners. While T2 time in whole brain held the greatest predict...
Source: Experimental Neurology - May 1, 2015 Category: Neurology Authors: Barry JM, Choy M, Dube C, Robbins A, Obenaus A, Lenck-Santini PP, Scott RC, Baram TZ, Holmes GL Tags: Exp Neurol Source Type: research

Desert Hedgehog is a Mediator of Demyelination in Compression Neuropathies.
Abstract The secreted protein desert hedgehog (dhh) controls the formation of the nerve perineurium during development and is a key component of Schwann cells that ensures peripheral nerve survival. We postulated that dhh may play a critical role in maintaining myelination and investigated its role in demyelination induced compression neuropathies by using a post-natal model of a chronic nerve injury in wildtype and dhh(-/-) mice. We evaluated demyelination using electrophysiological, morphological, and molecular approaches. Dhh transcripts and protein are down-regulated early after injury in wild-type mice, sugge...
Source: Experimental Neurology - April 30, 2015 Category: Neurology Authors: Jung J, Frump D, Su J, Wang W, Mozaffar T, Gupta R Tags: Exp Neurol Source Type: research

Endogenous neurogenic cell response in the mature mammalian brain following traumatic injury.
Abstract In the mature mammalian brain, new neurons are generated throughout life in the neurogenic regions of the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. Over the past two decades, extensive studies have examined the extent of adult neurogenesis in the SVZ and DG, the role of the adult generated new neurons in normal brain function and the underlying mechanisms regulating the process of adult neurogenesis. The extent and the function of adult neurogenesis under neuropathological conditions have also been explored in varying types of disease models in animals. Increasing evidence h...
Source: Experimental Neurology - April 30, 2015 Category: Neurology Authors: Sun D Tags: Exp Neurol Source Type: research

MFGE8/Integrin β3 Pathway Alleviates Apoptosis and Inflammation in Early Brain Injury after Subarachnoid Hemorrhage in Rats.
CONCLUSION: MFGE8 could alleviate neurologic damage in early brain injury after SAH via anti-inflammation and anti-apoptosis effects. MFGE8 may serve as a promising therapeutic target for future management of SAH patients. PMID: 25936875 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 30, 2015 Category: Neurology Authors: Liu F, Chen Y, Hu Q, Li B, Tang J, He Y, Guo Z, Feng H, Tang J, Zhang JH Tags: Exp Neurol Source Type: research

Cannabinoid functions in the amygdala contribute to conditioned fear memory in streptozotocin-induced diabetic mice: interaction with glutamatergic functions.
Abstract The role of cannabinoid systems in conditioned fear memory was investigated in streptozotocin (STZ)-induced diabetic mice. The cannabinoid receptor agonist WIN-55,212-2 (1 mg/kg, i.p.), when injected into normal mice after conditioning, significantly prolonged the duration of freezing behavior. This effect was significantly inhibited by the cannabinoid CB1 receptor antagonist AM 251 (3 mg/kg, s.c.), but not by the cannabinoid CB2 receptor antagonist AM 630 (1 mg/kg, s.c.). The duration of freezing in STZ-induced diabetic mice was significantly longer than that in non-diabetic mice. The injection of WIN-55...
Source: Experimental Neurology - April 27, 2015 Category: Neurology Authors: Ikeda H, Ikegami M, Kai M, Kamei J Tags: Exp Neurol Source Type: research

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA.
Abstract Transgenic expression of neurotrophic factors in skeletal muscle has been found to protect mice from neuromuscular disease, including spinal bulbar muscular atrophy (SBMA), triggering renewed interest in neurotrophic factors as therapeutic agents for treating neuromuscular disease. Because SBMA is an androgen-dependent disease, and brain-derived neurotrophic factor (BDNF) mediates effects of androgens on neuromuscular systems, we asked whether BDNF expression is impaired in two different transgenic (Tg) mouse models of SBMA, the so called "97Q" and "myogenic" SBMA models. The 97Q model...
Source: Experimental Neurology - April 27, 2015 Category: Neurology Authors: Halievski K, Henley CL, Domino L, Poort JE, Fu M, Katsuno M, Adachi H, Sobue G, Breedlove SM, Jordan CL Tags: Exp Neurol Source Type: research

The microRNAs Let7c and miR21 are recognized by neuronal toll-like receptor 7 to restrict dendritic growth of neurons.
Abstract Inflammatory responses are known to play critical roles in the regulation of neurodevelopment and neurodegeneration. Although microglial cells are recognized as professional immune cells in brains, recent evidence suggests that neurons also express important receptors and regulators of innate immunity, including toll-like receptor 7 (TLR7), which is a receptor for single-stranded RNAs (ssRNAs). Here, we report that neuronal TLR7 recognizes endogenous ligands such as the miRNAs Let7c and miR21 and play a negative role in controlling neuronal growth in a cell-autonomous manner. We show here that hippocampal...
Source: Experimental Neurology - April 24, 2015 Category: Neurology Authors: Liu HY, Huang CM, Hung YF, Hsueh YP Tags: Exp Neurol Source Type: research

The Influence of the Cage Environment on Rodent Physiology and Behavior: Implications for Reproducibility of Pre-Clinical Rodent Research.
Abstract The reproducibility of pre-clinical research is an important concern that is now being voiced by constituencies that include the National Institutes of Health, the pharmaceutical industry, Congress, the public and the scientific community. An important facet of performing and publishing wellcontrolled reproducible pre-clinical research is to stabilize and more completely define the environment of the animal subjects. Scientists who use rodents in research generally recognize the importance of maintaining a stable animal environment. However, despite a theoretical and general awareness of these issues, man...
Source: Experimental Neurology - April 22, 2015 Category: Neurology Authors: Toth LA Tags: Exp Neurol Source Type: research

Large Animal and Primate Models of Spinal Cord Injury for the Testing of Novel Therapies.
csis J, Lu P, Magnuson DS, Marsala M, Moore SW, Mothe AJ, Oudega M, Plant GW, Rabchevsky AS, Schwab JM, Silver J, Steward O, Xu XM, Guest JD, Tetzlaff W Abstract Large animal and primate models of spinal cord injury (SCI) are being increasingly utilized for the testing of novel therapies. While these represent intermediary animal species between rodents and humans and offer the opportunity to pose unique research questions prior to clinical trials, the role that such large animal and primate models should play in the translational pipeline is unclear. In this initiative we engaged members of the SCI research commu...
Source: Experimental Neurology - April 19, 2015 Category: Neurology Authors: Kwon BK, Streijger F, Hill CE, Anderson AJ, Bacon M, Beattie MS, Blesch A, Bradbury EJ, Brown A, Bresnahan JC, Case CC, Colburn RW, David S, Fawcett JW, Ferguson AR, Fischer I, Floyd CL, Gensel JC, Houle JD, Jakeman LB, Jeffery ND, Jones LA, Kleitman N, K Tags: Exp Neurol Source Type: research

Chondroitin Sulfate Proteoglycans: Key modulators in the Developing and Pathologic Central Nervous System.
Abstract Chondroitin Sulfate Proteoglycans (CSPGs) are a major component of the extracellular matrix in the central nervous system (CNS) and play critical role in the development and pathophysiology of the brain and spinal cord. Developmentally, CSPGs provide guidance cues for growth cones and contribute to the formation of neuronal boundaries in the developing CNS. Their presence in perineuronal nets plays a crucial role in the maturation of synapses and closure of critical periods by limiting synaptic plasticity. Following injury to the CNS, CSPGs are dramatically upregulated by reactive glia which form a glial ...
Source: Experimental Neurology - April 18, 2015 Category: Neurology Authors: Dyck SM, Karimi-Abdolrezaee S Tags: Exp Neurol Source Type: research

Ischemic conditioning-induced endogenous brain protection: Applications Pre-, Per- or Post-Stroke.
Abstract In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre- or post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stoke and traumatic brain injury. Recently, studies s...
Source: Experimental Neurology - April 18, 2015 Category: Neurology Authors: Wang Y, Reis C, Applegate R, Stier G, Martin R, Zhang JH Tags: Exp Neurol Source Type: research

Differential upregulation of the cannabinoid CB2 receptor in neurotoxic and inflammation-driven rat models of Parkinson's disease.
This study indicates that targeting the CB2 receptor may represent a viable target for anti-inflammatory disease modification in Parkinson's disease. PMID: 25895887 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 17, 2015 Category: Neurology Authors: Concannon RM, Okine BN, Finn DP, Dowd E Tags: Exp Neurol Source Type: research

Reduction of zinc accumulation in mitochondria contributes to decreased cerebral ischemic injury by normobaric hyperoxia treatment in an experimental stroke model.
In this study, we investigate whether NBO could regulate zinc accumulation in the penumbra and prevent mitochondrial damage in penumbral tissue using a transient cerebral ischemic rat model. Our results showed that NBO significantly reduced zinc staining positive cells and zinc-staining intensity in penumbral tissues, but not in the ischemic core. Moreover, ischemia-induced zinc accumulation in mitochondria, isolated from penumbral tissues, was greatly attenuated by NBO or a zinc specific chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). NBO or TPEN administration stabilized the mitochondrial membrane po...
Source: Experimental Neurology - April 16, 2015 Category: Neurology Authors: Dong W, Qi Z, Liang J, Shi W, Zhao Y, Luo Y, Ji X, Liu KJ Tags: Exp Neurol Source Type: research

Grafted murine induced pluripotent stem cells prevent death of injured rat motoneurons otherwise destined to die.
In this study the effects of undifferentiated murine iPSCs on damaged motoneurons were investigated following avulsion of the lumbar 4 (L4) ventral root, an injury known to induce the death of the majority of the affected motoneurons. Avulsion and reimplantation of the L4 ventral root (AR procedure) was accompanied by the transplantation of murine iPSCs into the injured spinal cord segment in rats. Control animals underwent ventral root avulsion and reimplantation, but did not receive iPSCs. The grafted iPSCs induced an improved reinnervation of the reimplanted ventral root by the host motoneurons as compared with the cont...
Source: Experimental Neurology - April 15, 2015 Category: Neurology Authors: Pajer K, Nemes C, Berzsenyi S, Kovács KA, Pirity MK, Pajenda G, Nógrádi A, Dinnyés A Tags: Exp Neurol Source Type: research

Interictal spike frequency varies with ovarian cycle stage in a rat nodel of epilepsy.
Abstract In catamenial epilepsy, seizures exhibit a cyclic pattern that parallels the menstrual cycle. Many studies suggest that catamenial seizures are caused by fluctuations in gonadal hormones during the menstrual cycle, but this has been difficult to study in rodent models of epilepsy because the ovarian cycle in rodents, called the estrous cycle, is disrupted by severe seizures. Thus, when epilepsy is severe, estrous cycles become irregular or stop. Therefore, we modified kainic acid (KA)- and pilocarpine-induced status epilepticus (SE) models of epilepsy so that seizures were rare for the first months after ...
Source: Experimental Neurology - April 9, 2015 Category: Neurology Authors: D'Amour J, Magagna-Poveda A, Moretto J, Friedman D, LaFrancois JJ, Pearce P, Fenton AA, MacLusky NJ, Scharfman HE Tags: Exp Neurol Source Type: research

Nerve regeneration: Specific metabolic demands?
PMID: 25864930 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - April 9, 2015 Category: Neurology Authors: Stassart RM, Nave KA Tags: Exp Neurol Source Type: research

Enhanced expression of matrix metalloproteinase-12 contributes to Npc1 deficiency-induced axonal degeneration.
Abstract Niemann-Pick type C (NPC) disease is a genetic disorder associated with intracellular cholesterol accumulation in brain and other organs, and neurodegeneration is generally believed to be the fatal cause of the disease. In view of the emerging role of matrix metalloproteinase-12 (MMP-12) in neuronal injury, we investigated its expression and potential roles in axonal degeneration in Npc1-/- mouse brain. Microarray and quantitative real-time reversed transcription PCR analysis indicated a marked increase in MMP-12 mRNA levels in cerebellum of 3 week-old Npc1-/- mice, as compared to wild-type littermates. W...
Source: Experimental Neurology - April 9, 2015 Category: Neurology Authors: Liao G, Wang Z, Lee E, Moreno S, Abuelnasr O, Baudry M, Bi X Tags: Exp Neurol Source Type: research

Chondroitin sulfate proteoglycans impede myelination by oligodendrocytes after perinatal white matter injury.
Abstract Hypomyelination is the major cause of neurodevelopmental deficits that are associated with perinatal white matter injury. Chondroitin sulfate proteoglycans (CSPGs) are known to exert inhibitory effects on the migration and differentiation of oligodendrocytes (OLs). However, few studies describe the roles of CSPGs in myelination by OLs and the cognitive dysfunction (CD) that follows perinatal white matter injury. Here, we examined the alterations in the expression of CSPGs and their functional impact on the maturation of OLs and myelination in a neonatal rat model of hypoxic-ischemic (HI) brain injury. Thr...
Source: Experimental Neurology - April 8, 2015 Category: Neurology Authors: Deng Y, Xu Q, Pei Y, Huang Z, Yang Z, Chen C Tags: Exp Neurol Source Type: research

Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar-like cultures.
Abstract The regenerative capacity of the adult CNS neurons after injury is strongly inhibited by the spinal cord lesion site environment that is composed primarily of the reactive astroglial scar and invading meningeal fibroblasts. Olfactory ensheathing cell (OEC) transplantation facilitates neuronal survival and functional recovery after a complete spinal cord transection, yet the mechanisms by which this recovery occurs remain unclear. We used a unique multicellular scar-like culture model to test if OECs promote neurite outgrowth in growth inhibitory areas. Astrocytes were mechanically injured and challenged b...
Source: Experimental Neurology - April 8, 2015 Category: Neurology Authors: Khankan RR, Wanner IB, Phelps PE Tags: Exp Neurol Source Type: research

Seizure Reduction through Interneuron-mediated Entrainment using Low Frequency Optical Stimulation.
Abstract Low frequency electrical stimulation (LFS) can reduce neural excitability and suppress seizures in animals and patients with epilepsy. However the therapeutic outcome could benefit from the determination of the cell types involved in seizure suppression. We used optogenetic techniques to investigate the role of interneurons in LFS (1Hz) in the epileptogenic hippocampus. Optical low frequency stimulation (oLFS) was first used to activate the cation channel channelrhodopsin-2 (ChR2) in the Thy1-ChR2 transgenic mouse that expresses ChR2 in both excitatory and inhibitory neurons. We found that oLFS could effe...
Source: Experimental Neurology - April 8, 2015 Category: Neurology Authors: Ladas TP, Chiang CC, Gonzalez-Reyes LE, Nowak T, Durand DM Tags: Exp Neurol Source Type: research

Studying Tauopathies in Drosophila: A Fruitful Model.
Abstract Tauopathies are a group of neurodegenerative disorders that include hereditary frontotemporal dementias (FTDs) such as FTD with parkinsonism linked to chromosome 17 (FTDP-17), as well as sporadic variants of FTDs like progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease. These diverse diseases all have in common the presence of abnormally phosphorylated tau aggregates. In this review, I will summarize key features of transgenic Drosophila models of tauopathies and a number of insights into disease mechanisms as well as therapeutic implications gained from the fruit fly...
Source: Experimental Neurology - April 7, 2015 Category: Neurology Authors: Sun M, Chen L Tags: Exp Neurol Source Type: research

Neurodevelopmental Implications of the General Anesthesia in Neonate and Infants.
Abstract Each year, about six million children, including 1.5 million infants, in the United States undergo surgery with general anesthesia, often requiring repeated exposures. However, a crucial question remains of whether neonatal anesthetics are safe for the developing central nervous system (CNS). General anesthesia encompasses the administration of agents that induce analgesic, sedative, and muscle relaxant effects. Although the mechanisms of action of general anesthetics are still not completely understood, recent data have suggested that anesthetics primarily modulate two major neurotransmitter receptor gro...
Source: Experimental Neurology - April 7, 2015 Category: Neurology Authors: Lee JH, Zhang J, Wei L, Yu SP Tags: Exp Neurol Source Type: research

Characterization and therapeutic evaluation of a Nestin(+) CNP(+) NG2(+) cell population on mouse spinal cord injury.
Abstract The NG2 chondroitin sulphate proteoglycan-expressing neural cells (NG2 cells) have originally been considered as oligodendrocyte progenitor cells (OPCs). However, recent findings on their diverse functions and lineage heterogeneity demonstrated that the NG2 cells contain various sub-populations whose concrete features and therapeutic potential yet remained elucidated. In the present study, we characterized a Nestin(+) 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) (+) NG2(+) subpopulation from embryonic rat cerebral cortex. The Nestin(+) CNP(+) NG2(+) cells exhibited remarkable progenitor characterist...
Source: Experimental Neurology - April 7, 2015 Category: Neurology Authors: Liu R, Zhang S, Yang H, Ju P, Xia Y, Shi Y, Lim TH, Lim AS, Liang F, Feng Z Tags: Exp Neurol Source Type: research

A novel function for Wnt signaling modulating neuronal firing activity and the temporal structure of spontaneous oscillation in the entorhinal-hippocampal circuit.
Abstract During early and late postnatal development, the establishment of functional neuronal connectivity depends on molecules like Wnt that help the recently formed synapses to establish and consolidate their new cellular interactions. However, unlike other molecules, whether Wnt can modulate the firing properties of cells is unknown. Here, for the first time we explore the physiological effect of the canonical and non-canonical Wnt pathways on a circuit that is currently generating oscillatory activity, the entorhinal cortex-hippocampal circuit. Our results indicate that Wnt pathways have strong influence in t...
Source: Experimental Neurology - April 6, 2015 Category: Neurology Authors: Oliva CA, Inestrosa NC Tags: Exp Neurol Source Type: research

Slit and semaphorin signaling governed by Islet transcription factors positions motor neuron somata within the neural tube.
Abstract Motor neurons send out axons to peripheral muscles while their cell bodies remain in the ventral spinal cord. The unique configuration of motor neurons spanning the border between the CNS and PNS has been explained by structural barriers such as boundary cap (BC) cells, basal lamina and radial glia. However, mechanisms in motor neurons that retain their position have not been addressed yet. Here we demonstrate that the Islet1 (Isl1) and Islet2 (Isl2) transcription factors, which are essential for acquisition of motor neuron identity, also contribute to restrict motor neurons within the neural tube. In mic...
Source: Experimental Neurology - April 2, 2015 Category: Neurology Authors: Lee H, Kim M, Kim N, Macfarlan T, Pfaff SL, Mastick GS, Song MR Tags: Exp Neurol Source Type: research

Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.
Abstract Functional recovery after peripheral nerve injury and surgical repair declines with time and distance because the injured neurons without target contacts (chronic axotomy) progressively lose their regenerative capacity and chronically denervated Schwann cells (SCs) atrophy and fail to support axon regeneration. Findings that brief low frequency electrical stimulation (ES) accelerates axon outgrowth and muscle reinnervation after immediate nerve surgery in rats and human patients suggest that ES might improve regeneration after delayed nerve repair. To test this hypothesis, common peroneal (CP) neurons wer...
Source: Experimental Neurology - April 1, 2015 Category: Neurology Authors: Elzinga K, Tyreman N, Ladak A, Savaryn B, Olson J, Gordon T Tags: Exp Neurol Source Type: research

Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal-prefrontal coherence.
Abstract Deep Brain Stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampu...
Source: Experimental Neurology - April 1, 2015 Category: Neurology Authors: Insel N, Pilkiw M, Nobrega JN, Hutchison WD, Takehara-Nishiuchi K, Hamani C Tags: Exp Neurol Source Type: research

White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke.
In conclusion, our studies suggest that the distal MCAO stroke model consistently results in ischemic brain injury with long-term behavioral deficits, and is therefore suitable for the evaluation of long-term stroke outcomes. Furthermore, aged mice exhibit deterioration of functional outcomes after stroke and this deterioration is linked to white matter damage and reductions in M2 microglia/macrophage polarization. PMID: 25836044 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 30, 2015 Category: Neurology Authors: Suenaga J, Hu X, Pu H, Shi Y, Hassan SH, Xu M, Leak RK, Stetler RA, Gao Y, Chen J Tags: Exp Neurol Source Type: research

Astrocyte roles in traumatic brain injury.
Abstract Astrocytes sense changes in neural activity and extracellular space composition. In response, they exert homeostatic mechanisms critical for maintaining neural circuit function, such as buffering neurotransmitters, modulating extracellular osmolarity and calibrating neurovascular coupling. In addition to upholding normal brain activities, astrocytes respond to diverse forms of brain injury with heterogeneous and progressive changes of gene expression, morphology, proliferative capacity and function that are collectively referred to as reactive astrogliosis. Traumatic brain injury (TBI) sets in motion comp...
Source: Experimental Neurology - March 28, 2015 Category: Neurology Authors: Burda JE, Bernstein AM, Sofroniew MV Tags: Exp Neurol Source Type: research

Brain Mitochondrial ATP-insensitive large conductance Ca(+2)-activated K(+) channel properties are altered in a rat model of amyloid-β neurotoxicity.
Brain Mitochondrial ATP-insensitive large conductance Ca(+2)-activated K(+) channel properties are altered in a rat model of amyloid-β neurotoxicity. Exp Neurol. 2015 Mar 28; Authors: Jafari A, Noursadeghi E, Khodagholi F, Saghiri R, Sauve R, Aliaghaei A, Eliassi A Abstract Mitochondrial dysfunction is a hallmark of amyloid-beta (Aβ)-induced neuronal toxicity in Alzheimer's disease (AD). However, the underlying mechanism of how Aβ affects mitochondrial function remains uncertain. Because mitochondrial potassium channels have been involved in several mitochondrial functions including cyt...
Source: Experimental Neurology - March 28, 2015 Category: Neurology Authors: Jafari A, Noursadeghi E, Khodagholi F, Saghiri R, Sauve R, Aliaghaei A, Eliassi A Tags: Exp Neurol Source Type: research

Granulocyte-colony stimulating factor activates JAK2/PI3K/PDE3B pathway to inhibit corticosterone synthesis in a neonatal hypoxic-ischemic brain injury rat model.
CONCLUSION: Our data suggest that the neuroprotective G-CSF reduces corticosterone synthesis at the adrenal level by degrading intracellular cAMP via activation of the JAK2/PI3K/PDE3B pathway. PMID: 25816736 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 25, 2015 Category: Neurology Authors: Charles MS, Drunalini Perera PN, Doycheva DM, Tang J Tags: Exp Neurol Source Type: research

Drosophila and experimental neurology in the post-genomic era.
Abstract For decades, the fruit fly, Drosophila melanogaster, has been among the premiere genetic model systems for probing fundamental neurobiology, including elucidation of mechanisms responsible for human neurologic disorders. Flies continue to offer virtually unparalleled versatility and speed for genetic manipulation, strong genomic conservation, and a nervous system that recapitulates a range of cellular and network properties relevant to human disease. I focus here on four critical challenges emerging from recent advances in our understanding of the genomic basis of human neurologic disorders where innovati...
Source: Experimental Neurology - March 24, 2015 Category: Neurology Authors: Shulman JM Tags: Exp Neurol Source Type: research

Post-trauma administration of the pifithrin-α oxygen analog improves histological and functional outcomes after experimental traumatic brain injury.
Post-trauma administration of the pifithrin-α oxygen analog improves histological and functional outcomes after experimental traumatic brain injury. Exp Neurol. 2015 Mar 24; Authors: Yang LY, Chu YH, Tweedie D, Yu QS, Pick CG, Hoffer BJ, Greig NH, Wang JY Abstract Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Programmed death of neuronal cells plays a crucial role in acute and chronic neurodegeneration following TBI. The tumor suppressor protein p53, a transcription factor, has been recognized as an important regulator of apoptotic neuronal death. The p53 inact...
Source: Experimental Neurology - March 24, 2015 Category: Neurology Authors: Yang LY, Chu YH, Tweedie D, Yu QS, Pick CG, Hoffer BJ, Greig NH, Wang JY Tags: Exp Neurol Source Type: research

Lesion-Induced Accumulation of Platelets Promotes Survival of Adult Neural Stem / Progenitor Cells.
In conclusion, our results show that platelet-derived compounds specifically promote SEZ-derived NSPC survival and suggest that platelets might contribute to the enlargement of the pool of SEZ NSPCs that are available for CNS repair in response to injury. PMID: 25819103 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 24, 2015 Category: Neurology Authors: Kazanis I, Feichtner M, Lange S, Rotheneichner P, Hainzl S, Öller M, Schallmoser K, Rohde E, Reitsamer HA, Couillard-Despres S, Bauer HC, Franklin RJ, Aigner L, Rivera FJ Tags: Exp Neurol Source Type: research

Demyelination as a rational therapeutic target for ischemic or traumatic brain injury.
Abstract Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination...
Source: Experimental Neurology - March 24, 2015 Category: Neurology Authors: Shi H, Hu X, Leak RK, Shi Y, An C, Suenaga J, Chen J, Gao Y Tags: Exp Neurol Source Type: research

Spreading depolarizations mediate excitotoxicity in the development of acute cortical lesions.
Abstract Spreading depolarizations (SD) are mass depolarizations of neurons and astrocytes that occur spontaneously in acute brain injury and mediate time-dependent lesion growth. Glutamate excitotoxicity has also been extensively studied as a mechanism of neuronal injury, although its relevance to in vivo pathology remains unclear. Here we hypothesized that excitotoxicity in acute lesion development occurs only as a consequence of SD. Using glutamate-sensitive microelectrodes, we found that SD induced by KCl in normal rat cortex elicits increases in extracellular glutamate (11.6±1.3μM) that are synchron...
Source: Experimental Neurology - March 24, 2015 Category: Neurology Authors: Hinzman JM, DiNapoli VA, Mahoney EJ, Gerhardt GA, Hartings JA Tags: Exp Neurol Source Type: research

Sphingosine kinase 1 mediates neuroinflammation following cerebral ischemia.
Abstract Sphingosine kinases (Sphks) are the rate-limiting kinases in the generation of sphingosine-1-phosphate, which is a well-established intracellular pro-survival lipid mediator. Sphk2 has been reported to be protective following experimental stroke. We investigated the role of Sphk1 in cerebral ischemia using a mouse middle cerebral artery occlusion (MCAO) model and an in vitro glucose-oxygen deprivation (OGD) model. Sphk expression and activity were assessed in the ischemic brain with quantitative PCR (qPCR), western blot, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Pharmacological a...
Source: Experimental Neurology - March 19, 2015 Category: Neurology Authors: Zheng S, Wei S, Wang X, Xu Y, Xiao Y, Liu H, Jia J, Cheng J Tags: Exp Neurol Source Type: research

The Secretome of Apoptotic Human Peripheral Blood Mononuclear Cells Attenuates Secondary Damage Following Spinal Cord Injury in Rats.
This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of ...
Source: Experimental Neurology - March 19, 2015 Category: Neurology Authors: Haider T, Höftberger R, Rüger B, Mildner M, Blumer R, Mitterbauer A, Buchacher T, Sherif C, Redl H, Gabriel C, Gyöngyösi M, Fischer MB, Lubec G, Ankersmit HJ Tags: Exp Neurol Source Type: research

Intranasal Delivery of Hypoxia-Preconditioned Bone Marrow-Derived Mesenchymal Stem Cells Enhanced Regenerative Effects after Intracerebral Hemorrhagic Stroke in Mice.
In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluatio...
Source: Experimental Neurology - March 19, 2015 Category: Neurology Authors: Sun J, Wei ZZ, Gu X, Zhang JY, Zhang Y, Li J, Wei L Tags: Exp Neurol Source Type: research

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors- recommendations for methods and experimental designs.
Abstract Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR form Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR ...
Source: Experimental Neurology - March 18, 2015 Category: Neurology Authors: Losen M, Martinez-Martinez P, Molenaar PC, Lazaridis K, Tzartos S, Brenner T, Duan RS, Luo J, Lindstrom J, Kusner L Tags: Exp Neurol Source Type: research

NMDA receptor blockade in the developing cortex induces autophagy-mediated death of immature cortical GABAergic interneurons: An ex vivo and in vivo study in Gad67-GFP mice.
kri S Abstract In neonates, excitotoxicity is a major process involved in hypoxic-ischemic brain lesions, and several research groups have suggested the use of NMDA antagonists for neuroprotection. However, despite their clinical interest, there is more and more evidence suggesting that, in the immature brain, these molecules exert deleterious actions on migrating GABAergic interneurons by suppressing glutamatergic trophic inputs. Consequently, preventing the side effects of NMDA antagonists would be therapeutically useful. Because macroautophagy is involved in the adaptive response to trophic deprivation, the aim...
Source: Experimental Neurology - March 17, 2015 Category: Neurology Authors: Roux C, Aligny C, Lesueur C, Girault V, Brunel V, Ramdani Y, Genty D, Driouich A, Laquerrière A, Marret S, Brasse-Lagnel C, Gonzalez BJ, Bekri S Tags: Exp Neurol Source Type: research

Molecular Regulators of Nerve Conduction - Lessons from Inherited Neuropathies and Rodent Genetic Models.
Abstract Myelinated nerve fibers are highly compartmentalized. Helically wrapped lipoprotein membranes of myelin are integrated with subsets of proteins specifically in each compartment to shape the physiological behavior of these nerve fibers. With the advance of molecular biology and genetics, many functions of these proteins have been revealed over the past decade. In this review, we will first discuss how action potential propagation has been understood by classical electrophysiological studies. In particular, the discussion will be concentrated on how the geometric dimensions of myelinated nerve fibers (such ...
Source: Experimental Neurology - March 16, 2015 Category: Neurology Authors: Li J Tags: Exp Neurol Source Type: research

Venous System in Acute Brain Injury: Mechanisms of Pathophysiological Change and Function.
Abstract Cerebral vascular injury is a major component of acute brain injury. Currently, neuroprotective strategies primarily focus on the recanalization of cerebral arteries and capillaries, and the protection of insulted neurons. Hitherto, the role of vein drainage in the pathophysiology of acute brain injury has been overlooked, due to an under appreciation of the magnitude of the impact of veins in circulation. In this review, we summarize the changes in the vein morphology and functions that are known, or likely to occur related to acute brain injury, and aim to advance the therapeutic management of acute bra...
Source: Experimental Neurology - March 14, 2015 Category: Neurology Authors: Chen S, Chen Y, Xu L, Matei N, Tang J, Feng H, Zhang J Tags: Exp Neurol Source Type: research

Moderate exercise training attenuates inflammatory mediators in DRG of Type 1 diabetic rats.
This study demonstrates the significance of moderate exercise in the amelioration of pain in animals with Type 1 diabetes after 6 weeks of exercise paradigm. After initial acclimatization, streptozotocin-diabetic animals were placed in motorized running wheels for sixty minutes per day, for five days a week for 6 weeks starting at one week after diabetes. A growing body of evidence suggests that the release of proinflammatory cytokines plays an important role in the development and persistence of pain. This study demonstrates that moderate exercise increases the expression of inhibitory neurotransmitter enkephalin and also...
Source: Experimental Neurology - March 14, 2015 Category: Neurology Authors: Yoon H, Thakur V, Isham D, Fayad M, Chattopadhyay M Tags: Exp Neurol Source Type: research