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

Use of cell-based assays in myasthenia gravis and other antibody-mediated diseases.
ent A Abstract The increasing demand on diagnostic assays that are sensitive and specific for pathogenic antibodies, and the interest in identifying new antigens, prompted the development of cell-based assays for the detection of autoantibodies in myasthenia gravis and other autoimmune disorders. Cell-based assays were initially used to show that clustering the AChR improved the positivity in myasthenia gravis, and similar assays have now been applied to detection of antibodies to neuromuscular junction candidate proteins such as LRP4 and agrin. In addition cell-based assays have been used in the routine detection...
Source: Experimental Neurology - March 14, 2015 Category: Neurology Authors: Rodriguez Cruz PM, Huda S, López-Ruiz P, Vincent A Tags: Exp Neurol Source Type: research

Suppression of Adenosine 2a Receptor (A2aR)-Mediated Adenosine Signaling Improves Disease Phenotypes in a Mouse Model of Amyotrophic Lateral Sclerosis.
Abstract Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease in which the majority of upper and lower motor neurons are degenerated. Despite intensive efforts to identify drug targets and develop neuroprotective strategies, effective therapeutics for ALS remains unavailable. The identification and characterization of novel targets and pathways remain crucial in the development of ALS therapeutics. Adenosine is a major neuromodulator that actively regulates synaptic transmission. Interestingly, adenosine levels are significantly elevated in the cerebrospinal fluid (CSF) of progres...
Source: Experimental Neurology - March 13, 2015 Category: Neurology Authors: Ng SK, Higashimori H, Tolman M, Yang Y Tags: Exp Neurol Source Type: research

ENU mutagenesis identifies mice modeling Warburg Micro syndrome with sensory axon degeneration caused by a deletion in Rab18.
Abstract Mutations in the gene of RAB18, a member of Ras superfamily of small G-proteins, cause Warburg Micro Syndrome (WARBM) which is characterized by defective neurodevelopmental and ophthalmological phenotypes. Despite loss of Rab18 had been reported to induce disruption of the endoplasmic reticulum structure and neuronal cytoskeleton organization, parts of the pathogenic mechanism caused by RAB18 mutation remains unclear. From the N-ethyl-N-nitrosourea (ENU)-induced mutagenesis library, we identified a mouse line whose Rab18 was knocked out. This Rab18(-/-) mouse exhibited stomping gait, smaller testis and ey...
Source: Experimental Neurology - March 13, 2015 Category: Neurology Authors: Cheng CY, Wu JC, Tsai JW, Nian FS, Wu PC, Kao LS, Fann MJ, Tsai SJ, Liou YJ, Tai CY, Hong CJ Tags: Exp Neurol Source Type: research

Increased Brain Bio-distribution and Chemical Stability and Decreased Immunogenicity of an Engineered Variant of GDNF.
Abstract Several lines of evidence indicate that Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for dopaminergic neurons. Direct parenchymal administration of GDNF is robustly neuroprotective and neurorestorative in multiple neurotoxin-based animal models (rat and non-human primate (NHP)) of Parkinson's Disease (PD), suggesting its potential as a therapeutic agent. Although small, open-label clinical trials of intra-putamenal administration of bacteria-derived, full length, wild type GDNF (GDNFwt) were efficacious in improving standardized behavioral scores, a double-blinded, randomized con...
Source: Experimental Neurology - March 12, 2015 Category: Neurology Authors: Smith RC, O'Bryan LM, Mitchell PJ, Leung D, Ghanem M, Wilson JM, Hanson JC, Sossick S, Cooper J, Huang L, Merchant KM, Lu J, O'Neill MJ Tags: Exp Neurol Source Type: research

Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke.
Abstract Stroke is a devastating neurological disease with no satisfactory therapies to preserve long-term neurological function, perhaps due to the sole emphasis on neuronal survival in most preclinical studies. Recent studies have revealed the importance of protecting multiple cell types in the injured brain, such as oligodendrocytes and components of the neurovascular unit, before long-lasting recovery of function can be achieved. For example, revascularization in the ischemic penumbra is critical to provide various neurotrophic factors that enhance the survival and activity of neurons and other progenitor cell...
Source: Experimental Neurology - March 12, 2015 Category: Neurology Authors: Zhang W, Wang H, Zhang H, Leak RK, Shi Y, Hu X, Gao Y, Chen J Tags: Exp Neurol Source Type: research

Diffuse and persistent blood-spinal cord barrier disruption after contusive spinal cord injury rapidly recovers following intravenous infusion of bone marrow mesenchymal stem cells.
Abstract Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to reduce the severity of experimental spinal cord injury (SCI), but mechanisms are not fully understood. One important consequence of SCI is damage to the microvasculature and disruption of the blood spinal cord barrier (BSCB). In the present study we induced a contusive SCI at T9 in the rat and studied the effects of intravenous MSC infusion on BSCB permeability, microvascular architecture and locomotor recovery over a 10 week period. Intravenously delivered MSCs could not be identified in the spinal cord, but distributed primarily to ...
Source: Experimental Neurology - March 12, 2015 Category: Neurology Authors: Matsushita T, Lankford KL, Arroyo EJ, Sasaki M, Neyazi M, Radtke C, Kocsis JD Tags: Exp Neurol Source Type: research

Spinal RyR2 pathway regulated by the RNA-binding protein HuD induces pain hypersensitivity in antiretroviral neuropathy.
Abstract The antiretroviral toxic neuropathy, a distal sensory polyneuropathy associated with antiretroviral treatment, is a frequently occurring neurological complication during treatment of patients with AIDS and often leads to discontinuation of antiretroviral therapy. The mechanisms by which antiretroviral drugs contribute to the development of neuropathic pain are not known. Using drugs that reduce intracellular calcium ions (Ca(2+)), we investigated the hypothesis that altered cytosolic Ca(2+) concentration contributes to the 2',3'-dideoxycytidine (ddC)-evoked painful neuropathy. Administration of ddC induce...
Source: Experimental Neurology - March 9, 2015 Category: Neurology Authors: Sanna MD, Peroni D, Quattrone A, Ghelardini C, Galeotti N Tags: Exp Neurol Source Type: research

A balanced view of choroid plexus structure and function: Focus on adult humans.
Abstract Recently tremendous progress has been made in studying choroid plexus (CP) physiology and pathophysiology; and correcting several misconceptions about the CP. Specifically, the details of how CP, a locus of the blood-CSF barrier (BCSFB), secretes and purifies CSF, generates intracranial pressure (ICP), maintains CSF ion homeostasis, and provides micronutrients, proteins and hormones for neuronal and glial development, maintenance and function, are being understood on a molecular level. Unequivocal evidence that the CP secretory epithelium is the predominant supplier of CSF for the ventricles comes from mu...
Source: Experimental Neurology - March 4, 2015 Category: Neurology Authors: Spector R, Keep RF, Robert Snodgrass S, Smith QR, Johanson CE Tags: Exp Neurol Source Type: research

Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats.
This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage. PMID: 25749188 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 4, 2015 Category: Neurology Authors: Ni W, Okauchi M, Hatakeyama T, Gu Y, Keep RF, Xi G, Hua Y Tags: Exp Neurol Source Type: research

PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine.
In conclusion, the lack of PI3Kγ revealed a deleterious effect in an animal model of convulsions induced by pilocarpine, suggesting that this enzyme may play a protective role in seizures and pathological outcomes associated with this condition. PMID: 25749189 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 4, 2015 Category: Neurology Authors: de Assis Lima IV, Campos AC, Miranda AS, Marciano ÉL, Amaral-Martins F, Vago JP, de Melo RP, de Sousa LP, Vieira LB, Teixeira MM, Fiebich BL, Moraes MF, Teixeira AL, de Oliveira AC Tags: Exp Neurol Source Type: research

Mirror-image pain after nerve reconstruction in rats is related to enhanced density of epidermal peptidergic nerve fibers.
Abstract Mirror-image pain is a phenomenon in which unprovoked pain is detected on the uninjured contralateral side after unilateral nerve injury. Although it has been implicated that enhanced production of nerve growth factor (NGF) in the contralateral dorsal root ganglion is important in the development of mirror-image pain, it is not known if this is related to enhanced expression of nociceptive fibers in the contralateral skin. Mechanical and thermal sensitivity in the contralateral hind paw was measured at four different time points (5, 10, 20 and 30 weeks) after transection and immediate end-to-end reconstru...
Source: Experimental Neurology - March 4, 2015 Category: Neurology Authors: Kambiz S, Brakkee EM, Duraku LS, Hovius SE, Ruigrok TH, Walbeehm ET Tags: Exp Neurol Source Type: research

The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.
This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE,PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24hrs and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 2...
Source: Experimental Neurology - March 3, 2015 Category: Neurology Authors: Collins JM, King AE, Woodhouse A, Kirkcaldie MT, Vickers JC Tags: Exp Neurol Source Type: research

Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model - recommendations for methods and experimental designs.
Abstract Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector m...
Source: Experimental Neurology - March 2, 2015 Category: Neurology Authors: Kusner LL, Losen M, Vincent A, Lindstrom J, Tzartos S, Lazaridis K, Martinez-Martinez P Tags: Exp Neurol Source Type: research

Evidence for the role of Phosphatidylcholine-Specific Phospholipase in experimental subarachnoid hemorrhage in rats.
In conclusion, our data suggest that PC-PLC participates in SAH-induced EBI. PMID: 25743218 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 2, 2015 Category: Neurology Authors: Li B, Li H, Wang Z, Wang Y, Gao A, Cui Y, Liu Y, Chen G Tags: Exp Neurol Source Type: research

Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection.
Abstract In order to determine if the functional changes in the GABAergic system in the trigeminal spinal subnucleus caudalis (Vc) are involved in the mechanisms underlying extraterritorial neuropathic pain in the orofacial region following inferior alveolar nerve transection (IANX), mechanical noxious behavior, phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry and single neuronal activity were analyzed in vesicular GABA transporter (VGAT)-VenusA rats expressing fluorescent protein and the VGAT in Vc neurons. The number of VGAT-VenusA positive neurons was significantly reduced in IAN...
Source: Experimental Neurology - February 28, 2015 Category: Neurology Authors: Okada-Ogawa A, Nakaya Y, Imamura Y, Kobayashi M, Shinoda M, Kita K, Sessle BJ, Iwata K Tags: Exp Neurol Source Type: research

It might be time to let cooler heads prevail after mild traumatic brain injury or concussion.
PMID: 25732932 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 27, 2015 Category: Neurology Authors: Kochanek PM, Jackson TC Tags: Exp Neurol Source Type: research

Dimethyl fumarate attenuates cerebral edema formation by protecting the blood-brain barrier integrity.
Abstract Brain edema is a hallmark of various neuropathologies, but the underlying mechanisms are poorly understood. We aim to characterize how tissue hypoxia, together with oxidative stress and inflammation, leads to capillary dysfunction and breakdown of the blood-brain barrier (BBB). In a mouse stroke model we show that systemic treatment with dimethyl fumarate (DMF), an antioxidant drug clinically used for psoriasis and multiple sclerosis, significantly prevented edema formation in vivo. Indeed, DMF stabilized the BBB by preventing disruption of interendothelial tight junctions and gap formation, and decreased...
Source: Experimental Neurology - February 25, 2015 Category: Neurology Authors: Kunze R, Urrutia A, Hoffmann A, Liu H, Helluy X, Pham M, Reischl S, Korff T, Marti HH Tags: Exp Neurol Source Type: research

Development of Stage-Dependent Glycans on the Fc domains of IgG Antibodies of ALS Animals.
Abstract We recently revealed a unique glycan on the Fc domain of IgG antibodies in ALS patients that mediates antibody-dependent cell cytotoxicity (ADCC). This glycan has a bi-antennary structure that lacks the core fucose and sialic acid residues but contains a bisecting GlcNAc (A2BG2). Little is known, however, about the incidence of A2BG2 expression and IgG cytotoxicity under ALS conditions within well-defined clinical stages. Here, we characterize the IgG antibodies produced in ALS Tg mice by detecting intra- and extra-cellular antigens of motor neurons that express different glycan patterns during the diseas...
Source: Experimental Neurology - February 25, 2015 Category: Neurology Authors: Edri-Brami M, Sharoni H, Hayoun D, Skutelsky L, Nemirovsky A, Porgador A, Lichtenstein RG Tags: Exp Neurol Source Type: research

Regeneration of sensory but not motor axons following visceral nerve injury.
In conclusion, our results show that visceral sensory and motor neurons have a different capacity to regenerate axons following axotomy, however in both components of the circuit uninjured bladder neurons spontaneously grow new axon collaterals to replace the lost terminal field within the organ. For a full functional recovery, understanding the environmental and cellular mechanisms that reduce the ability of pelvic ganglion cells to undergo axonal regeneration is needed. PMID: 25725351 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 25, 2015 Category: Neurology Authors: Payne SC, Belleville PJ, Keast JR Tags: Exp Neurol Source Type: research

Statistical Considerations for Preclinical Studies.
Abstract Research studies must always have proper planning, conduct, analysis and reporting in order to preserve scientific integrity. Preclinical studies, the first stage of the drug development process, are no exception to this rule. The decision to advance to clinical trials in humans rely on the results of these studies. Recent observations show that a significant number of preclinical studies lack rigor in their conduct and reporting. This paper discusses statistical aspects, such as design, sample size determination, and methods of analyses, that will help add rigor and improve the quality of preclinical stu...
Source: Experimental Neurology - February 25, 2015 Category: Neurology Authors: Aban IB, George B Tags: Exp Neurol Source Type: research

Reduced photoreceptor death and improved retinal function during retinal degeneration in mice lacking innate immunity adaptor protein MyD88.
Abstract The injury inflammatory response mediated by the innate immune system is an important contributor to neurodegeneration in the central nervous system (CNS) and retina. A major branch of the innate immune system is regulated by the Toll-like receptors (TLRs), which are receptors for endogenous damage associated molecules released from injured cells as well as pathogen-derived molecules, and interleukin-1 receptors (IL-1R), which are activated by IL-1α, IL-1β and IL-18 cytokines. TLRs and IL-1R are expressed on immune and non-immune cell types and act as first responders to cell damage, which resu...
Source: Experimental Neurology - February 25, 2015 Category: Neurology Authors: Syeda S, Patel AK, Lee T, Hackam AS Tags: Exp Neurol Source Type: research

Pharmacologically Induced Hypothermia Attenuates Traumatic Brain Injury in Neonatal Rats.
Abstract Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic b...
Source: Experimental Neurology - February 25, 2015 Category: Neurology Authors: Gu X, Wei ZZ, Espinera A, Lee JH, Ji X, Wei L, Dix TA, Yu SP Tags: Exp Neurol Source Type: research

Impact of treatment duration and lesion size on effectiveness of chondroitinase treatment post-SCI.
Abstract The effects of 2weeks of intralesional chondroitinase abc (ch'abc) treatment on anatomical plasticity and behavioral recovery are examined in adult cats and compared to results achieved with 4weeks of treatment following tightly controlled lateral hemisection injuries. Analyses also were completed using 35 cats with a range of hemisection magnitudes to assess relationships between treatment duration, lesion size and functional recovery. Results indicate that both 2 and 4weeks of treatment significantly increased the number of rubrospinal tract (RuST) neurons with axons below the lesion, but neither affect...
Source: Experimental Neurology - February 25, 2015 Category: Neurology Authors: Mondello SE, Jefferson SC, Tester NJ, Howland DR Tags: Exp Neurol Source Type: research

Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice.
Abstract Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTEN(loxP/loxP) mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; control...
Source: Experimental Neurology - February 20, 2015 Category: Neurology Authors: Danilov CA, Steward O Tags: Exp Neurol Source Type: research

The pattern of Fos expression in the rat auditory brainstem changes with the temporal structure of binaural electrical intracochlear stimulation.
RB Abstract The immediate-early-gene c-fos with its protein product Fos has been used as a powerful tool to investigate neuronal activity and plasticity following sensory stimulation. Fos combines with Jun, another IEG product, to form the dimeric transcription factor activator protein 1 (AP-1) which has been implied in a variety of cellular functions like neuronal plasticity, apoptosis, and regeneration. The intracellular emergence of Fos indicates a functional state of nerve cells directed towards molecular and morphological changes. The central auditory system is construed to detect stimulus intensity, spectra...
Source: Experimental Neurology - February 20, 2015 Category: Neurology Authors: Jakob TF, Döring U, Illing RB Tags: Exp Neurol Source Type: research

NMDA receptor triggered molecular cascade underlies compression-induced rapid dendritic spine plasticity in cortical neurons.
Abstract Compression causes the reduction of dendritic spines of underlying adult cortical pyramidal neurons but the mechanisms remain at large. Using a rat epidural cerebral compression model, dendritic spines on the more superficial-lying layer III pyramidal neurons were found quickly reduced in 12hours, while those on the deep-located layer V pyramidal neurons were reduced slightly later, starting 1day following compression. No change in the synaptic vesicle markers synaptophysin and vesicular glutamate transporter 1 suggest no change in afferents. Postsynaptically, N-methyl-D-aspartate (NMDA) receptor traffick...
Source: Experimental Neurology - February 20, 2015 Category: Neurology Authors: Chen LJ, Wang YJ, Chen JR, Tseng GF Tags: Exp Neurol Source Type: research

TGF-β1 prevents blood-brain barrier damage and hemorrhagic transformation after thrombolysis in rats.
TGF-β1 prevents blood-brain barrier damage and hemorrhagic transformation after thrombolysis in rats. Exp Neurol. 2015 Feb 20; Authors: Cai Y, Liu X, Chen W, Wang Z, Xu G, Zeng Y, Ma Y Abstract Transforming growth factor-beta1 (TGF-β1) is well known to promote extracellular matrix accumulation. Recent studies demonstrated that TGF-β1 protects against blood-brain barrier (BBB) disruption in the condition of inflammatory pain and stroke. In the present study, we investigated whether TGF-β1 can maintain BBB integrity and prevent hemorrhagic transformation (HT) after recombinant tissue...
Source: Experimental Neurology - February 20, 2015 Category: Neurology Authors: Cai Y, Liu X, Chen W, Wang Z, Xu G, Zeng Y, Ma Y Tags: Exp Neurol Source Type: research