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Experimental Neurology

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https://www.readbyqxmd.com/read/28192079/electrical-neuromodulation-of-the-cervical-spinal-cord-facilitates-forelimb-skilled-function-recovery-in-spinal-cord-injured-rats
#1
Monzurul Alam, Guillermo Garcia-Alias, Benita Jin, Jonathan Keyes, Hui Zhong, Roland R Roy, Yury Gerasimenko, Daniel C Lu, V Reggie Edgerton
Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats...
February 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28189729/progressive-leukoencephalopathy-impairs-neurobehavioral-development-in-sialin-deficient-mice
#2
Stijn Stroobants, Nathalie G G Van Acker, Frans W Verheijen, Ilse Goris, Guy F T Daneels, Rachel Schot, Elly Verbeek, Michiel W M Knaapen, An De Bondt, Hinrich W Göhlmann, Marion L A Crauwels, Grazia M S Mancini, Luc J Andries, Dieder W E Moechars, Rudi D'Hooge
Slc17a5(-/-) mice represent an animal model for the infantile form of sialic acid storage disease (SASD). We analyzed genetic and histological time-course expression of myelin and oligodendrocyte (OL) lineage markers in different parts of the CNS, and related this to postnatal neurobehavioral development in these mice. Sialin-deficient mice display a distinct spatiotemporal pattern of sialic acid storage, CNS hypomyelination and leukoencephalopathy. Whereas few genes are differentially expressed in the perinatal stage (p0), microarray analysis revealed increased differential gene expression in later postnatal stages (p10-p18)...
February 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28189728/optimization-of-trophic-support-for-neural-stem-cell-grafts-in-sites-of-spinal-cord-injury
#3
Jacob Robinson, Paul Lu
Previously we utilized fibrin matrices and a cocktail of nine growth factors and a cell death inhibitor to promote survival and fill of neural stem cell (NSC) or neural progenitor cell (NPC) grafts to sites of spinal cord injury (SCI). In the current study, we examined whether the number of growth factors in a supportive matrix could be reduced to a more clinically practical number while retaining extensive NPC survival and fill of a spinal cord lesion site. NPCs derived from embryonic day 14 Fischer 344 rat spinal cords expressing green fluorescent protein (GFP) were embedded in fibrin matrices containing a defined growth factor cocktail: one to four factors were tested among nine different groups...
February 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28179153/activation-of-npffr2-leads-to-hyperalgesia-through-the-spinal-inflammatory-mediator-cgrp-in-mice
#4
Ya-Tin Lin, Ho-Ling Liu, Yuan-Ji Day, Che-Chien Chang, Po-Hung Hsu, Jin-Chung Chen
Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared to WT mice...
February 5, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28174025/effects-of-liposome-based-local-suppression-of-nerve-growth-factor-in-the-bladder-on-autonomic-dysreflexia-during-urinary-bladder-distention-in-rats-with-spinal-cord-injury
#5
Katsumi Kadekawa, Tsuyoshi Yoshizawa, Naoki Wada, Takahiro Shimizu, Tsuyoshi Majima, Pradeep Tyagi, William C de Groat, Kimio Sugaya, Naoki Yoshimura
PURPOSE: To examine (1) whether spinal cord injury (SCI) time-dependently increases the severity of autonomic dysreflexia (AD) and expression levels of bladder nerve growth factor (NGF) protein, and (2) whether local suppression of NGF in the bladder improves SCI-induced AD in rats. MATERIALS AND METHODS: SCI was produced by the transection of the T2/3 spinal cord in female Sprague-Dawley rats. At 4 or 8weeks after SCI, differences in the mean arterial blood pressure (ΔMAP) and heart rate (ΔMHR) during graded increases in intravesical pressure to 20, 40 and 60cm H2O from those before bladder distention and NGF protein levels in the bladder wall were evaluated in spinal intact and SCI rats under urethane anesthesia...
February 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28163161/zebrafish-models-of-autism-spectrum-disorder
#6
REVIEW
Daria A Meshalkina, Marina N Kizlyk, Elana V Kysil, Adam D Collier, David J Echevarria, Murilo S Abreu, Leonardo J G Barcellos, Cai Song, Jason E Warnick, Evan J Kyzar, Allan V Kalueff
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by motor, social and cognitive deficits that develop early during childhood. The pathogenesis of ASD is not well characterized and involves a multifaceted interaction between genetic, neurobiological and environmental factors. Animal (experimental) models possess evolutionarily conserved behaviors and molecular pathways that are highly relevant for studying ASD. The zebrafish (Danio rerio) is a relatively new animal model with promise for understanding the pathogenesis of complex brain disorders and discovering novel treatments...
February 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28163159/mitochondrial-ferritin-protects-sh-sy5y-cells-against-h2o2-induced-oxidative-stress-and-modulates-%C3%AE-synuclein-expression
#7
Hongpeng Guan, Hongkuan Yang, Mingchun Yang, Daijiro Yanagisawa, Jean-Pierre Bellier, Masaki Mori, Shogo Takahata, Takashi Nonaka, Shiguang Zhao, Ikuo Tooyama
Mitochondrial ferritin (FtMt) is a type of ferritin that sequesters iron. Previous studies have shown that FtMt is expressed by dopaminergic neurons in the substantia nigra and that it may be involved in the pathology of Parkinson's disease. However, the functional roles of FtMt in dopaminergic neurons remain unclear. In this study, we investigated the function of FtMt in α-synuclein regulation and its antioxidant roles in dopaminergic cells using human dopaminergic neuroblastoma cells, SH-SY5Y. In physiological conditions, FtMt knockdown increased α-synuclein expression at the protein level but not at the mRNA level...
February 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28163160/transplanted-human-glial-restricted-progenitors-can-rescue-the-survival-of-dysmyelinated-mice-independent-of-the-production-of-mature-compact-myelin
#8
Agatha Lyczek, Antje Arnold, Jiangyang Zhang, James T Campanelli, Miroslaw Janowski, Jeff W M Bulte, Piotr Walczak
The therapeutic effect of glial progenitor transplantation in diseases of dysmyelination is currently attributed to the formation of new myelin. Using magnetic resonance imaging (MRI), we show that the therapeutic outcome in dysmyelinated shiverer mice is dependent on the extent of cell migration but not the presence of mature and compact myelin. Human or mouse glial restricted progenitors (GRPs) were transplanted into rag2(-/)(-) shiverer mouse neonates and followed for over one year. Mouse GRPs produced mature myelin as detected with multi-parametric MRI, but showed limited migration without extended animal lifespan...
February 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28163158/neuron-subset-specific-pten-deletion-induces-abnormal-skeletal-activity-in-mice
#9
Joaquin N Lugo, Marjorie H Thompson, Philippe Huber, Gregory Smith, Ronald Y Kwon
Individuals with a history of epilepsy are at higher risk for bone fractures compared to the general population. Although clinical studies support an association between low bone mineral density (BMD) and anti-seizure medications, little is known on whether a history of seizures is linked to altered bone health. Therefore, in this study we tested the hypothesis that bone mass, morphology, and bone mineralization are altered by seizures in genetically epileptic animals and in animals subjected to an episode of status epilepticus...
February 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28161255/neurovascular-uncoupling-in-the-triple-transgenic-model-of-alzheimer-s-disease-impaired-cerebral-blood-flow-response-to-neuronal-derived-nitric-oxide-signaling
#10
Cátia F Lourenço, Ana Ledo, Rui M Barbosa, João Laranjinha
Nitric oxide (NO)-dependent pathways and cerebrovascular dysfunction have been shown to contribute to the cognitive decline and neurodegeneration observed in Alzheimer's disease (AD) but whether they represent initial factors or later changes of the disease is still a matter of debate. In this work, we aimed at investigating whether and to what extent neuronal-derived NO signaling and related neurovascular coupling are impaired along aging in the hippocampus of the triple transgenic mouse model of Alzheimer's Disease (3xTg-AD)...
February 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28131725/the-5-alpha-reductase-inhibitor-finasteride-reduces-dyskinesia-in-a-rat-model-of-parkinson-s-disease
#11
Roberto Frau, Paola Savoia, Silvia Fanni, Chiara Fiorentini, Camino Fidalgo, Elisabetta Tronci, Roberto Stancampiano, Mario Meloni, Antonino Cannas, Francesco Marrosu, Marco Bortolato, Paola Devoto, Cristina Missale, Manolo Carta
Levodopa-induced dyskinesia (LID) is a disabling motor complication occurring in Parkinson's disease patients (PD) after long-term l-DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5-alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor-selective and non-selective agonists, without inducing extrapyramidal symptoms...
January 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28131727/long-term-protective-effects-of-aav9-mesencephalic-astrocyte-derived-neurotrophic-factor-gene-transfer-in-parkinsonian-rats
#12
Fei Hao, Chun Yang, Sha-Sha Chen, Yan-Yan Wang, Wei Zhou, Qiang Hao, Tao Lu, Barry Hoffer, Li-Ru Zhao, Wei-Ming Duan, Qun-Yuan Xu
Intrastriatal injection of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein has been shown to provide neuroprotective and neurorestorative effects in a 6-hydroxydopamine (6-OHDA) - lesioned rat model of Parkinson's disease. Here, we used an adeno-associated virus serotype 9 (AAV9) vector to deliver the human MANF (hMANF) gene into the rat striatum 10days after a 6-OHDA lesion to examine long-term effects of hMANF on nigral dopaminergic neurons and mechanisms underlying MANF neuroprotection...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28131726/transplantation-site-influences-the-phenotypic-differentiation-of-dopamine-neurons-in-ventral-mesencephalic-grafts-in-parkinsonian-rats
#13
Marija Fjodorova, Eduardo M Torres, Stephen B Dunnett
Foetal midbrain progenitors have been shown to survive, give rise to different classes of dopamine neurons and integrate into the host brain alleviating Parkinsonian symptoms following transplantation in patients and animal models of the disease. Dopamine neuron subpopulations in the midbrain, namely A9 and A10, can be identified anatomically based on cell morphology and ascending axonal projections. G protein-gated inwardly rectifying potassium channel Girk2 and the calcium binding protein Calbindin are the two best available histochemical markers currently used to label (with some overlap) A9- and A10-like dopamine neuron subtypes, respectively, in tyrosine hydroxylase expressing neurons both in the midbrain and grafts...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28131724/insights-in-spatio-temporal-characterization-of-human-fetal-neural-stem-cells
#14
Raquel Martín-Ibáñez, Inés Guardia, Mónica Pardo, Cristina Herranz, Rike Zietlow, Ngoc-Nga Vinh, Anne Rosser, Josep M Canals
Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental stages: 4-5, 6-7 and 8-9weeks post conception (wpc) and four brain areas: forebrain, cortex, whole ganglionic eminence (WGE) and cerebellum...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28111229/surgical-repair-in-humans-after-traumatic-nerve-injury-provides-limited-functional-neural-regeneration-in-adults
#15
REVIEW
Winnie A Palispis, Ranjan Gupta
Traumatic nerve injuries result in devastating loss of neurologic function with unpredictable functional recovery despite optimal medical management. After traumatic nerve injury and denervation, regenerating axons must traverse a complex environment in which they encounter numerous barriers on the way to reinnervation of their target muscle. Outcomes of surgical intervention alone have unfortunately reached a plateau, resulting in often unsatisfactory functional recovery. Over the past few decades, many improvements were developed to supplement and boost the results of surgical repair...
January 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28110076/facilitation-of-distinct-inhibitory-synaptic-inputs-by-chemical-anoxia-in-neurons-in-the-oculomotor-facial-and-hypoglossal-motor-nuclei-of-the-rat
#16
Satoshi Takagi, Yu Kono, Masashi Nagase, Soichiro Mochio, Fusao Kato
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the brainstem and spinal cord. Clinical studies have indicated that there is a distinct region-dependent difference in the vulnerability of motor neurons. For example, the motor neurons in the facial and hypoglossal nuclei are more susceptible to neuronal death than those in the oculomotor nucleus. To understand the mechanism underlying the differential susceptibility to cell death of the neurons in different motor nuclei, we compared the effects of chemical anoxia on the membrane currents and postsynaptic currents in different motor nuclei...
January 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28081963/rapid-neuroinflammatory-response-localized-to-injured-neurons-after-diffuse-traumatic-brain-injury-in-swine
#17
Kathryn L Wofford, James P Harris, Kevin D Browne, Daniel P Brown, Michael R Grovola, Constance J Mietus, John A Wolf, John E Duda, Mary E Putt, Kara L Spiller, D Kacy Cullen
Despite increasing appreciation of the critical role that neuroinflammatory pathways play in brain injury and neurodegeneration, little is known about acute microglial reactivity following diffuse traumatic brain injury (TBI) - the most common clinical presentation that includes all concussions. Therefore, we investigated acute microglial reactivity using a porcine model of closed-head rotational velocity/acceleration-induced TBI that closely mimics the biomechanical etiology of inertial TBI in humans. We observed rapid microglial reactivity within 15min of both mild and severe TBI...
January 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28077335/omega-3-fatty-acids-regulate-nlrp3-inflammasome-activation-and-prevent-behavior-deficits-after-traumatic-brain-injury
#18
Chao Lin, Honglu Chao, Zheng Li, Xiupeng Xu, Yinlong Liu, Zhongyuan Bao, Lijun Hou, Yan Liu, Xiaoming Wang, Yongping You, Ning Liu, Jing Ji
Omega-3 fatty acids (ω-3 FAs) attenuate inflammation and improve neurological outcome in response to traumatic brain injury (TBI), but the specific anti-inflammatory mechanisms remain to be elucidated. Here we found that NLRP3 inflammasome and subsequent pro-inflammatory cytokines were activated in human brains after TBI. Rats treated with ω-3 FAs had significantly less TBI-induced caspase-1 cleavage and IL-1β secretion than those with vehicle. G protein-coupled receptor 40 (GPR40) was observed to be involved in this anti-inflammation...
January 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28077334/the-neuroprotective-compound-p7c3-a20-promotes-neurogenesis-and-improves-cognitive-function-after-ischemic-stroke
#19
Zachary B Loris, Andrew A Pieper, W Dalton Dietrich
Ischemic stroke is a devastating condition with few therapeutic interventions available. The neuroprotective compound P7C3-A20 inhibits mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute injury. P7C3 compounds enhance flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The effectiveness of P7C3-A20 treatment on chronic histopathological and behavioral outcomes and neurogenesis after ischemic stroke has not previously been established...
January 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28077261/ventral-medullary-control-of-rapid-eye-movement-sleep-and-atonia
#20
Michael C Chen, Ramalingam Vetrivelan, Chun-Ni Guo, Catie Chang, Patrick M Fuller, Jun Lu
Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep...
January 7, 2017: Experimental Neurology
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