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Experimental Neurology

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https://www.readbyqxmd.com/read/28716559/optic-nerve-regeneration-in-mammals-regenerated-or-spared-axons
#1
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
https://www.readbyqxmd.com/read/28716558/emmprin-overexpression-in-svz-neural-progenitor-cells-increases-their-migration-towards-ischemic-cortex
#2
Michiko Kanemitsu, Oleg Tsupykov, Gaël Potter, Michael Boitard, Patrick Salmon, Eloisa Zgraggen, Eduardo Gascon, Galina Skibo, Alexandre G Dayer, Jozsef Z Kiss
Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system...
July 14, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28711506/sodium-selenate-activated-wnt-%C3%AE-catenin-signaling-and-repressed-amyloid-%C3%AE-formation-in-a-triple-transgenic-mouse-model-of-alzheimer-s-disease
#3
Na Jin, Huazhang Zhu, Xiao Liang, Wei Huang, Qingguo Xie, Peng Xiao, Jiazuan Ni, Qiong Liu
Accumulating evidences show that selenium dietary intake is inversely associated with the mortality of Alzheimer's disease (AD). Sodium selenate has been reported to reduce neurofibrillary tangles (NFT) in the tauopathic mouse models, but its effects on the Wnt/β-catenin signaling pathway and APP processing remain unknown during AD formation. In this paper, triple transgenic AD mice (3×Tg-AD) had been treated with sodium selenate in drinking water for 10month before the detection of hippocampal pathology...
July 12, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28698032/beyond-infection-maternal-immune-activation-by-environmental-factors-microglial-development-and-relevance-for-autism-spectrum-disorders
#4
REVIEW
Staci D Bilbo, Carina L Block, Jessica L Bolton, Richa Hanamsagar, Phuong K Tran
Immune molecules such as cytokines and chemokines and the cells that produce them within the brain, notably microglia, are critical for normal brain development. This recognition has in recent years led to the working hypothesis that inflammatory events during pregnancy, e.g. in response to infection, may disrupt the normal expression of immune molecules during critical stages of neural development and thereby contribute to the risk for neurodevelopmental disorders such as autism spectrum disorder (ASD). This hypothesis has in large part been shepherded by the work of Dr...
July 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28698031/comparable-impediment-of-cognitive-function-in-female-and-male-rats-subsequent-to-daily-administration-of-haloperidol-after-traumatic-brain-injury
#5
Kristin E Free, Anna M Greene, Corina O Bondi, Naima Lajud, Patricia B de la Tremblaye, Anthony E Kline
Antipsychotic drugs, such as haloperidol (HAL), are prescribed in the clinic to manage traumatic brain injury (TBI)-induced agitation. While preclinical studies have consistently shown that once-daily administration of HAL hinders functional recovery after TBI in male rats, its effects in females are unknown. Hence, the objective of this study was to directly compare neurobehavioral and histological outcomes in both sexes to determine whether the reported deleterious effects of HAL extend to females. Anesthetized adult female and male rats received either a controlled cortical impact (CCI) or sham injury and then were randomly assigned to a dosing regimen of HAL (0...
July 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28698030/myelination-of-axons-emerging-from-neural-progenitor-grafts-after-spinal-cord-injury
#6
Matthew Hunt, Paul Lu, Mark H Tuszynski
Neural progenitor cells (NPCs) grafted to sites of spinal cord injury (SCI) extend numerous axons over long distances and form new synaptic connections with host neurons. In the present study we examined the myelination of axons emerging from NPC grafts. Rat embryonic day 14 (E14) multipotent NPCs constitutively expressing GFP were grafted into adult C5 spinal cord hemisection lesions; 3months later we examined graft-derived axonal diameter and myelination using transmission electron microscopy. 104 graft-derived axons were characterized...
July 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28698029/critical-role-of-epha4-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rat
#7
Ruiming Fan, Budbazar Enkhjargal, Richard Camara, Feng Yan, Lei Gong, ShengtaoYao, Jiping Tang, Yangmei Chen, John H Zhang
Early brain injury (EBI) is reported as a primary cause of mortality in subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been associated with blood-brain barrier integrity and pro-apoptosis. We aimed to investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male adult Sprague-Dawley rats were randomly divided into sham versus endovascular perforation model of SAH groups. SAH grade, neurological score, Evans blue dye extravasation, brain water content, mortality, Fluoro-Jade staining, immunofluorescence staining, and western blot experiments were performed after SAH...
July 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28684211/age-related-accumulation-of-phosphorylated-mitofusin-2-protein-in-retinal-ganglion-cells-correlates-with-glaucoma-progression
#8
Mary P Nivison, Nolan G Ericson, Virginia M Green, Jason H Bielas, Jean S Campbell, Philip J Horner
Dysregulation of axonal bioenergetics is likely a key mechanism in the initiation and progression of age-related neurodegenerative diseases. Glaucoma is a quintessential neurodegenerative disorder characterized by progressive deterioration of the optic nerve (ON) and eventual death of retinal ganglion cells (RGCs). Age and elevation of intraocular pressure are key risk factors in glaucoma, but the common early hallmarks of decreased axonal transport and increased bioenergetic vulnerability likely underlie disease initiation...
July 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28679106/macrophage-migration-inhibitory-factor-a-multifaceted-cytokine-implicated-in-multiple-neurological-diseases
#9
REVIEW
Marcel F Leyton-Jaimes, Joy Kahn, Adrian Israelson
Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated...
July 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28669743/evidence-that-activation-of-p2x7r-does-not-exacerbate-neuronal-death-after-optic-nerve-transection-and-focal-cerebral-ischemia-in-mice
#10
Berrak Caglayan, Ahmet B Caglayan, Mustafa C Beker, Esra Yalcin, Merve Beker, Taha Kelestemur, Elif Sertel, Gürkan Ozturk, Ulkan Kilic, Fikrettin Sahin, Ertugrul Kilic
Conflicting data in the literature about the function of P2X7R in survival following ischemia necessitates the conductance of in-depth studies. To investigate the impacts of activation vs inhibition of the receptor on neuronal survival as well as the downstream signaling cascades, in addition to optic nerve transection (ONT), 30min and 90min of middle cerebral artery occlusion (MCAo) models were performed in mice. Intracellular calcium levels were assessed in primary cortical neuron cultures. Here, we show that P2X7R antagonist Brilliant Blue G (BBG) decreased DNA fragmentation, infarct volume, brain swelling, neurological deficit scores and activation of microglial cells after focal cerebral ischemia...
June 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28668375/transient-receptor-potential-melastatin-2-channels-trpm2-mediate-neonatal-hypoxic-ischemic-brain-injury-in-mice
#11
Sammen Huang, Ekaterina Turlova, Feiya Li, Mei-Hua Bao, Vivian Szeto, Raymond Wong, Ahmed Abussaud, Haitao Wang, Shuzhen Zhu, Xinzheng Gao, Yasuo Mori, Zhong-Ping Feng, Hong-Shuo Sun
Transient receptor potential melastatin 2 (TRPM2), a calcium-permeable non-selective cation channel, is reported to mediate brain damage following ischemic insults in adult mice. However, the role of TRPM2 channels in neonatal hypoxic-ischemic brain injury remains unknown. We hypothesize that TRPM2(+/-) and TRPM2(-/-) neonatal mice have reduced hypoxic-ischemic brain injury. To study the effect of TRPM2 on neonatal brain damage, we used 2,3,5-triphenyltetrazolium chloride (TTC) staining to assess the infarct volume and whole brain imaging to assess morphological changes in the brain...
June 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28658605/sociability-impairments-in-genetic-absence-epilepsy-rats-from-strasbourg-reversal-by-the-t-type-calcium-channel-antagonist-z944
#12
Mark T Henbid, Wendie N Marks, Madeline J Collins, Stuart M Cain, Terrance P Snutch, John G Howland
Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neural circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3...
June 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28645526/injury-induced-gp130-cytokine-signaling-in-peripheral-ganglia-is-reduced-in-diabetes-mellitus
#13
Jon P Niemi, Angela R Filous, Alicia DeFrancesco, Jane A Lindborg, Nisha A Malhotra, Gina N Wilson, Bowen Zhou, Samuel D Crish, Richard E Zigmond
Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia...
June 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28625590/intranasal-cotinine-improves-memory-and-reduces-depressive-like-behavior-and-gfap-cells-loss-induced-by-restraint-stress-in-mice
#14
Nelson Perez-Urrutia, Cristhian Mendoza, Nathalie Alvarez-Ricartes, Patricia Oliveros-Matus, Florencia Echeverria, J Alex Grizzell, George E Barreto, Alexandre Iarkov, Valentina Echeverria
Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP+ immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress...
June 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28624361/low-intensity-rtms-has-sex-dependent-effects-on-the-local-response-of-glia-following-a-penetrating-cortical-stab-injury
#15
Darren Clarke, Marissa A Penrose, Alan R Harvey, Jennifer Rodger, Kristyn A Bates
Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma...
June 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28622913/targeting-urate-to-reduce-oxidative-stress-in-parkinson-disease
#16
REVIEW
Grace F Crotty, Alberto Ascherio, Michael A Schwarzschild
Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants...
June 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28622912/clinical-approaches-to-the-development-of-a-neuroprotective-therapy-for-pd
#17
REVIEW
C W Olanow, K Kieburtz, R Katz
The development of a neuroprotective or disease-modifying therapy is the major unmet need in the management of Parkinson's Disease (PD) and the goal of much clinical and scientific research. However, despite enormous efforts and expense, no disease-modifying therapy for PD has been approved to date. Historically attempts to define such a therapy have been limited by confounding symptomatic/pharmacologic effects of the study intervention and the lack of a clear and well-defined regulatory and clinical development pathway that leads to a disease-modifying indication...
June 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28610844/overexpression-of-eif4f-components-in-meningiomas-and-suppression-of-meningioma-cell-growth-by-inhibiting-translation-initiation
#18
Janet L Oblinger, Sarah S Burns, Jie Huang, Li Pan, Yulin Ren, Rulong Shen, A Douglas Kinghorn, D Bradley Welling, Long-Sheng Chang
Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-eukaryotic translation initiation factor 4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knockdown of these proteins strongly reduced cell proliferation...
June 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28606623/the-interaction-between-alpha-7-nicotinic-acetylcholine-receptor-and-nuclear-peroxisome-proliferator-activated-receptor-%C3%AE-represents-a-new-antinociceptive-signaling-pathway-in-mice
#19
Giulia Donvito, Deniz Bagdas, Wisam Toma, Elnaz Rahimpour, Asti Jackson, Julie A Meade, Shakir AlSharari, Abhijit R Kulkarni, F Ivy Carroll, Aron H Lichtman, Roger L Papke, Ganesh A Thakur, M Imad Damaj
Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca(2+)-dependent manner...
June 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28602834/cns-disease-diminishes-the-therapeutic-functionality-of-bone-marrow-mesenchymal-stem-cells
#20
Alex Sargent, Lianhua Bai, Genevieve Shano, Molly Karl, Eric Garrison, Lahiru Ranasinghe, Sarah M Planchon, Jeffrey Cohen, Robert H Miller
Mesenchymal stem cells (MSCs) have emerged as a potentially powerful cellular therapy for autoimmune diseases including multiple sclerosis (MS). Based on their success in treating animal models of MS like experimental autoimmune encephalomyelitis (EAE), MSCs have moved rapidly into clinical trials for MS. The majority of these trials use autologous MSCs derived from MS patients, although it remains unclear how CNS disease may affect these cells. Here, we report that bone marrow MSCs derived from EAE mice lack therapeutic efficacy compared to naïve MSCs in their ability to ameliorate EAE...
June 9, 2017: Experimental Neurology
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