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Experimental Neurology

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https://www.readbyqxmd.com/read/28803751/insulin-prevents-aberrant-mitochondrial-phenotype-in-sensory-neurons-of-type-1-diabetic-rats
#1
Mohamad-Reza Aghanoori, Darrell R Smith, Subir Roy Chowdhury, Mohammad Golam Sabbir, Nigel A Calcutt, Paul Fernyhough
Diabetic neuropathy affects approximately 50% of diabetic patients. Down-regulation of mitochondrial gene expression and function has been reported in both human tissues and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin signaling in diabetes contributes to loss of mitochondrial function in DRG neurons and to development of neuropathy. Sensory neurons obtained from age-matched adult control or streptozotocin (STZ)-induced type 1 diabetic rats were cultured with or without insulin before determining mitochondrial respiration and expression of mitochondrial respiratory chain and insulin signaling-linked proteins...
August 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28803750/motor-cortex-and-spinal-cord-neuromodulation-promote-corticospinal-tract-axonal-outgrowth-and-motor-recovery-after-cervical-contusion-spinal-cord-injury
#2
N Zareen, M Shinozaki, D Ryan, H Alexander, A Amer, D Truong, N Khadka, A Sarkar, S Naeem, M Bikson, J Martin
Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement...
August 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28802980/corrigendum-to-sealing-frequency-of-b104-cells-declines-exponentially-with-decreasing-transection-distance-from-the-axon-hillock-exp-neurol-279-2016-149-158
#3
Christopher H McGill, Solomon Raju Bhupanapadu Sunkesula, Andrew D Poon, Michelle Mikesh, George D Bittner
No abstract text is available yet for this article.
August 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28802560/traumatic-brain-injuries-during-development-disrupt-dopaminergic-signaling
#4
Kate Karelina, Kristopher R Gaier, Zachary M Weil
Traumatic brain injuries (TBI) sustained during peri-adolescent development produce lasting neuro-behavioral changes that render individuals at an increased risk for developing substance abuse disorders. Experimental and clinical evidence of a prolonged period of hypodopaminergia after TBI have been well documented, but the effect of juvenile TBI on dopaminergic dysfunction and its relationship with substance abuse have not been investigated. In order to determine the effect of juvenile brain injury on dopaminergic signaling, female mice were injured at 21days of age and then beginning seven weeks later were assessed for behavioral sensitization to amphetamine, a drug that increases synaptic dopamine availability...
August 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28797631/hspb1-mutations-causing-hereditary-neuropathy-in-humans-disrupt-non-cell-autonomous-protection-of-motor-neurons
#5
Patrick L Heilman, SungWon Song, Carlos J Miranda, Kathrin Meyer, Amit K Srivastava, Amy Knapp, Christopher G Wier, Brian K Kaspar, Stephen J Kolb
Heat shock protein beta-1 (HSPB1), is a ubiquitously expressed, multifunctional protein chaperone. Mutations in HSPB1 result in the development of a late-onset, distal hereditary motor neuropathy type II (dHMN) and axonal Charcot-Marie Tooth disease with sensory involvement (CMT2F). The functional consequences of HSPB1 mutations associated with hereditary neuropathy are unknown. HSPB1 also displays neuroprotective properties in many neuronal disease models, including the motor neuron disease amyotrophic lateral sclerosis (ALS)...
August 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28780195/calcium-mitochondrial-dysfunction-and-slowing-the-progression-of-parkinson-s-disease
#6
REVIEW
D James Surmeier, Glenda M Halliday, Tanya Simuni
Parkinson's disease is characterized by progressively distributed Lewy pathology and neurodegeneration. The motor symptoms of cPD are unequivocally linked to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several features of these neurons appear to make them selectively vulnerable to factors thought to cause cPD, like aging, genetic mutations and environmental toxins. Among these features, Ca(2+) entry through Cav1 channels is particularly amenable to pharmacotherapy in early stage cPD patients...
August 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28774750/advances-in-nonhuman-primate-models-of-autism-integrating-neuroscience-and-behavior
#7
REVIEW
M D Bauman, C S Schumann
Given the prevalence and societal impact of autism spectrum disorders (ASD), there is an urgent need to develop innovative preventative strategies and treatments to reduce the alarming number of cases and improve core symptoms for afflicted individuals. Translational efforts between clinical and preclinical research are needed to (i) identify and evaluate putative causes of ASD, (ii) determine the underlying neurobiological mechanisms, (iii) develop and test novel therapeutic approaches and (iv) ultimately translate basic research into safe and effective clinical practices...
July 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28764903/achieving-neuroprotection-with-lrrk2-kinase-inhibitors-in-parkinson-disease
#8
REVIEW
Andrew B West
In the translation of discoveries from the laboratory to the clinic, the track record in developing disease-modifying therapies in neurodegenerative disease is poor. A carefully designed development pipeline built from discoveries in both pre-clinical models and patient populations is necessary to optimize the chances for success. Genetic variation in the leucine-rich repeat kinase two gene (LRRK2) is linked to Parkinson disease (PD) susceptibility. Pathogenic mutations, particularly those in the LRRK2 GTPase (Roc) and COR domains, increase LRRK2 kinase activities in cells and tissues...
July 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28764902/experimental-animal-models-of-parkinson-s-disease-a-transition-from-assessing-symptomatology-to-%C3%AE-synuclein-targeted-disease-modification
#9
REVIEW
Wai Kin D Ko, Erwan Bezard
With the understanding that α-synuclein plays a major role in the pathogenesis of Parkinson's disease (PD), novel animal models have been developed for conducting preclinical research in screening novel disease modifying therapies. Advancements in research techniques in α-synuclein targeted disease modification have utilised methods such as viral mediated expression of human α-synuclein, as well as the inoculation of pathogenic α-synuclein species from Lewy Bodies of PD patients, for accurately modelling progressive self-propagating neurodegeneration...
July 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28760579/survival-of-ipsc-derived-grafts-within-the-striatum-of-immunodeficient-mice-importance-of-developmental-stage-of-both-transplant-and-host-recipient
#10
Colton M Tom, Shahab Younesi, Elana Meer, Catherine Bresee, Marlesa Godoy, Virginia B Mattis
Degeneration of the striatum can occur in multiple disorders with devastating consequences for the patients. Infantile infections with streptococcus, measles, or herpes can cause striatal necrosis associated with dystonia or dyskinesia; and in patients with Huntington's disease the striatum undergoes massive degeneration leading to behavioral, psychological and movement issues, ultimately resulting in death. Currently, only supportive therapies are available for striatal degeneration. Clinical trials have shown some efficacy using transplantation of fetal-derived primary striatal progenitors...
July 28, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28757259/endotoxemia-induces-lung-brain-coupling-and-multi-organ-injury-following-cerebral-ischemia-reperfusion
#11
Nguyen Mai, Landa Prifti, Aric Rininger, Hannah Bazarian, Marc W Halterman
Post-ischemic neurodegeneration remains the principal cause of mortality following cardiac resuscitation. Recent studies have implicated gastrointestinal ischemia in the sepsis-like response associated with the post-cardiac arrest syndrome (PCAS). However, the extent to which the resulting low-grade endotoxemia present in up to 86% of resuscitated patients affects cerebral ischemia-reperfusion injury has not been investigated. Here we report that a single injection of low-dose lipopolysaccharide (50μg/kg, IP) delivered after global cerebral ischemia (GCI) induces blood-brain barrier permeability, microglial activation, cortical injury, and functional decline in vivo, compared to ischemia alone...
July 28, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28757258/bdnf-over-expression-induces-striatal-serotonin-fiber-sprouting-and-increases-the-susceptibility-to-l-dopa-induced-dyskinesia-in-6-ohda-lesioned-rats
#12
Elisabetta Tronci, Francesco Napolitano, Ana Muñoz, Camino Fidalgo, Francesca Rossi, Anders Björklund, Alessandro Usiello, Manolo Carta
In addition to its role in neuronal survival, the brain neurotrophic factor (BDNF) has been shown to influence serotonin transmission and synaptic plasticity, events strongly implicated in the appearance of l-DOPA-induced dyskinesia (LID), a motor complication occurring in parkinsonian patients after long-term treatment with the dopamine precursor. In order to evaluate a possible influence of BDNF in the appearance of LID, 6-OHDA-lesioned rats received a striatal injection of different concentrations of an adeno-associated viral (AAV) vector over-expressing either BDNF or GFP, as control vector...
July 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28756201/multiple-mild-traumatic-brain-injury-in-the-rat-produces-persistent-pathological-alterations-in-the-brain
#13
Diane M Brooks, Sarjubhai A Patel, Eric D Wohlgehagen, Erin O Semmens, Alan Pearce, Edmond A Sorich, Thomas F Rau
Multiple mild traumatic brain injury (mmTBI), in certain cases, produces persistent symptoms. However, the molecular mechanisms underlying these symptoms remain unclear. Here, we demonstrate extended pathological changes in the rat brain following mmTBI. Using the lateral fluid percussion (LFP) technique we exposed adult male Wistar rats to a mild TBI (mTBI) once a week for four weeks and compared them to surgical shams. At 90days following the last TBI or sham procedure the animals were cognitively tested in the Morris Water Maze (MWM), euthanized, and the brains removed for immunohistochemistry...
July 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28756200/erbb4-protects-against-neuronal-apoptosis-via-activation-of-yap-pik3cb-signaling-pathway-in-a-rat-model-of-subarachnoid-hemorrhage
#14
Feng Yan, Xiaoxiao Tan, Weifeng Wan, Brandon J Dixon, Ruiming Fan, Budbazar Enkhjargal, Qian Li, Jianmin Zhang, Gao Chen, John H Zhang
Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Previous studies indicated that ErbB4 (EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) is essential for normal development and maintenance of the nervous system. In this study, we explored the neuroprotective effects of ErbB4 and its downstream YAP (yes-associated protein)/PIK3CB signaling pathway in early brain injury after SAH in a rat model using the endovascular perforation method...
July 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28754506/the-differentiated-networks-related-to-essential-tremor-onset-and-its-amplitude-modulation-after-alcohol-intake
#15
David J Pedrosa, Christian Nelles, Peter Brown, Lukas J Volz, Esther A Pelzer, Marc Tittgemeyer, John-Stuart Brittain, Lars Timmermann
The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate...
July 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28746827/monocyte-depletion-early-after-stroke-promotes-neurogenesis-from-endogenous-neural-stem-cells-in-adult-brain
#16
Cecilia Laterza, Somsak Wattananit, Naomi Uoshima, Ruimin Ge, Daniel Tornero, Emanuela Monni, Olle Lindvall, Zaal Kokaia
Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances striatal neurogenesis at one week post-insult, most likely by increasing short-term survival of the newly formed neuroblasts in the SVZ and adjacent striatum...
July 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28734788/neuropathic-pain-in-experimental-autoimmune-neuritis-is-associated-with-altered-electrophysiological-properties-of-nociceptive-drg-neurons
#17
Omneya Taha, Thoralf Opitz, Marcus Mueller, Julika Pitsch, Albert Becker, Bernd Oliver Evert, Heinz Beck, Monika Jeub
Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers...
July 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28729113/activation-of-rage-stat3-pathway-by-methylglyoxal-contributes-to-spinal-central-sensitization-and-persistent-pain-induced-by-bortezomib
#18
Jia-You Wei, Cui-Cui Liu, Han-Dong Ouyang, Chao Ma, Man-Xiu Xie, Meng Liu, Wan-Long Lei, Huan-Huan Ding, Shao-Ling Wu, Wen-Jun Xin
Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats...
July 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28729114/altered-intrinsic-functional-connectivity-in-the-latent-period-of-epileptogenesis-in-a-temporal-lobe-epilepsy-model
#19
Hyoin Lee, Seungmoon Jung, Peter Lee, Yong Jeong
The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition...
July 17, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28716559/optic-nerve-regeneration-in-mammals-regenerated-or-spared-axons
#20
REVIEW
Dietmar Fischer, Alan R Harvey, Vincent Pernet, Vance P Lemmon, Kevin K Park
Intraorbital optic nerve crush in rodents is widely used as a model to study axon regeneration in the adult mammalian central nervous system. Recent studies using appropriate genetic manipulations have revealed remarkable abilities of mature retinal ganglion cell (RGC) axons to regenerate after optic nerve injury, with some studies demonstrating that axons can then go on to re-innervate a number of central visual targets with partial functional restoration. However, one confounding factor inherent to optic nerve crush injury is the potential incompleteness of the initial lesion, leaving spared axons that later on could erroneously be interpreted as regenerating distal to the injury site...
July 14, 2017: Experimental Neurology
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