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Remyelination

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https://www.readbyqxmd.com/read/29779852/treatment-of-progressive-multiple-sclerosis-challenges-and-promising-perspectives
#1
REVIEW
E Maillart
Management of progressive multiple sclerosis (MS) is one of the main challenges of the new century. Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod…); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin…). Nevertheless, despite recent promising positive clinical trials, new methodological approaches for therapeutic protocols with adaptable outcomes to assess progression are still needed.
May 17, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29775564/the-antibody-rhigm22-facilitates-hippocampal-remyelination-and-ameliorates-memory-deficits-in-the-cuprizone-mouse-model-of-demyelination
#2
Charlene Cui, Jing Wang, Ariana P Mullin, Anthony O Caggiano, Tom J Parry, Raymond W Colburn, Elias Pavlopoulos
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the CNS. In addition to motor, sensory and visual deficits, MS is also characterized by hippocampal demyelination and memory impairment. We recently demonstrated that a recombinant human-derived monoclonal IgM antibody, which is designated rHIgM22 and currently in clinical development for people with MS, accelerates remyelination of the corpus callosum in the brains of cuprizone-treated mice. Here, we investigated the effects of rHIgM22 in the hippocampus and on hippocampal-dependent learning and memory in the same mouse model of cuprizone-induced demyelination and spontaneous remyelination...
May 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29772247/internode-length-is-reduced-during-myelination-and-remyelination-by-neurofilament-medium-phosphorylation-in-motor-axons
#3
Eric Villalón, Devin M Barry, Nathan Byers, Katie Frizzi, Maria R Jones, Dan S Landayan, Jeffrey M Dale, Natalie L Downer, Nigel A Calcutt, Michael L Garcia
The distance between nodes of Ranvier, referred to as internode length, positively correlates with axon diameter, and is optimized during development to ensure maximal neuronal conduction velocity. Following myelin loss, internode length is reestablished through remyelination. However, remyelination results in short internode lengths and reduced conduction rates. We analyzed the potential role of neurofilament phosphorylation in regulating internode length during remyelination and myelination. Following ethidium bromide induced demyelination, levels of neurofilament medium (NF-M) and heavy (NF-H) phosphorylation were unaffected...
May 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29751775/cxcl12-engineered-endothelial-progenitor-cells-enhance-neurogenesis-and-angiogenesis-after-ischemic-brain-injury-in-mice
#4
Yaning Li, Shuang Chang, Wanlu Li, Guanghui Tang, Yuanyuan Ma, Yanqun Liu, Fang Yuan, Zhijun Zhang, Guo-Yuan Yang, Yongting Wang
BACKGROUND: Ischemic stroke causes a multitude of brain damage. Neurovascular injury and myelin sheath degradation are two manifestations of ischemic brain damage. Therapeutic strategies aiming only at repairing the neural components or the vessels cannot efficiently restore neurological function. Endothelial progenitor cells (EPCs) have the advantages of both promoting angiogenesis and secreting trophic factors that would promote neurogenesis. Chemokine cxcl12 gene therapy has also been shown to promote angiogenesis, neurogenesis, and remyelination, attracting EPCs, neural progenitor cells, and oligodendrocyte progenitor cells (OPCs) to the injured sites of the brain...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29744572/protective-potential-of-dimethyl-fumarate-in-a-mouse-model-of-thalamocortical-demyelination
#5
Manuela Cerina, Venu Narayanan, Anna Delank, Patrick Meuth, Stephanie Graebenitz, Kerstin Göbel, Alexander M Herrmann, Stefanie Albrecht, Thiemo Daldrup, Thomas Seidenbecher, Ali Gorji, Tanja Kuhlmann, Heinz Wiendl, Christoph Kleinschnitz, Erwin J Speckmann, Hans-Christian Pape, Sven G Meuth, Thomas Budde
Alterations in cortical cellular organization, network functionality, as well as cognitive and locomotor deficits were recently suggested to be pathological hallmarks in multiple sclerosis and corresponding animal models as they might occur following demyelination. To investigate functional changes following demyelination in a well-defined, topographically organized neuronal network, in vitro and in vivo, we focused on the primary auditory cortex (A1) of mice in the cuprizone model of general de- and remyelination...
May 9, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29742495/progressive-degeneration-and-inhibition-of-peripheral-nerve-regeneration-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#6
Binbin Deng, Wenjing Lv, Weisong Duan, Yakun Liu, Zhongyao Li, Yanqin Ma, Guisen Zhang, Xueqin Song, Can Cui, Xiaoming Qi, Yuan Li, Chunyan Li
BACKGROUND: Myelination, degeneration and regeneration are implicated in crucial responses to injury in the peripheral nervous system. Considering the progression of amyotrophic lateral sclerosis (ALS), we used the superoxide dismutase 1 (SOD1)-G93A transgenic mouse model of ALS to investigate the effects of mutant SOD1 on the peripheral nerves. METHODS: Changes in peripheral nerve morphology were analyzed in SOD1 mutant mice at various stages of the disease by toluidine blue staining and electron microscopy (EM)...
May 4, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29728852/glial-cells-shape-pathology-and-repair-after-spinal-cord-injury
#7
REVIEW
Andrew D Gaudet, Laura K Fonken
Glial cell types were classified less than 100 years ago by del Rio-Hortega. For instance, he correctly surmised that microglia in pathologic central nervous system (CNS) were "voracious monsters" that helped clean the tissue. Although these historical predictions were remarkably accurate, innovative technologies have revealed novel molecular, cellular, and dynamic physiologic aspects of CNS glia. In this review, we integrate recent findings regarding the roles of glia and glial interactions in healthy and injured spinal cord...
May 4, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29724768/identification-of-chronic-active-multiple-sclerosis-lesions-on-3t-mri
#8
M Absinta, P Sati, A Fechner, M K Schindler, G Nair, D S Reich
BACKGROUND AND PURPOSE: MR imaging-pathologic studies have reported that paramagnetic rims on 7T susceptibility-based MR imaging identify, in vivo, the subset of MS lesions with compartmentalized inflammation at the lesion edge and associated remyelination failure. Here, we assessed the reliability of detecting these rims on high-resolution 3T phase images. MATERIALS AND METHODS: High-resolution T2* and phase MR imaging was collected in 20 patients with MS at 3T (3D segmented EPI, 0...
May 3, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29722306/dissecting-the-multifactorial-nature-of-demyelinating-disease
#9
REVIEW
Karolina Kucharova, William B Stallcup
Chondroitin sulfate proteoglycan-4 (CSPG4) is a surface component of two key cell types (oligodendrocyte progenitor cells (OPCs) and myeloid cells) present in lysolecithin-induced lesions in mouse spinal cord. Two types of CSPG4 manipulations have been used to study the roles of these cells in myelin damage and repair: (1) OPC and myeloid-specific ablation of CSPG4, and (2) transplantation of enhanced green fluorescent protein (EGFP)-labeled progenitors to distinguish between bone marrow-derived macrophages and resident microglia...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29721326/axonal-regeneration-in-zebrafish-spinal-cord
#10
REVIEW
Sukla Ghosh, Subhra Prakash Hui
In the present review we discuss two interrelated events-axonal damage and repair-known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish...
March 2018: Regeneration
https://www.readbyqxmd.com/read/29720228/characterization-of-a-murine-mixed-neuron-glia-model-and-cellular-responses-to-regulatory-t-cell-derived-factors
#11
Marie Dittmer, Andrew Young, Thomas O'Hagan, George Eleftheriadis, Peter Bankhead, Yvonne Dombrowski, Reinhold J Medina, Denise C Fitzgerald
One of the unmet clinical needs in demyelinating diseases such as Multiple Sclerosis (MS) is to provide therapies that actively enhance the process of myelin regeneration (remyelination) in the central nervous system (CNS). Oligodendrocytes, the myelinating cells of the CNS, play a central role in remyelination and originate from oligodendrocyte progenitor cells (OPCs). We recently showed that depletion of regulatory T cells (Treg) impairs remyelination in vivo, and that Treg-secreted factors directly enhance oligodendrocyte differentiation...
May 2, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29719281/expression-of-nrf2-promotes-schwann-cell-mediated-sciatic-nerve-recovery-in-diabetic-peripheral-neuropathy
#12
Wei Tang, Xiangfang Chen, Haoqi Liu, Qian Lv, Junjie Zou, Yongquan Shi, Zhimin Liu
BACKGROUND/AIMS: High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth...
April 26, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29712789/macrophage-depletion-ameliorates-peripheral-neuropathy-in-aging-mice
#13
Xidi Yuan, Dennis Klein, Susanne Kerscher, Brian L West, Joachim Weis, Istvan Katona, Rudolf Martini
Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57Bl6 mice of either sex show similar pathological alterations as nerves from aging human individuals while 12 months old adult mice lack such alterations. Specifically, nerve fibers showed de- and remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of pre-synaptic markers, associated with α-bungarotoxin-positive postsynapses...
April 30, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29712487/prospective-study-of-myelin-water-fraction-changes-after-mild-traumatic-brain-injury-in-collegiate-contact-sports
#14
Heather S Spader, Douglas C Dean, W Curt LaFrance, Neha P Raukar, G Rees Cosgrove, Stephanie A Eyerly-Webb, Anna Ellermeier, Stephen Correia, Sean C L Deoni, Jeffrey Rogg
OBJECTIVE Mild traumatic brain injury (mTBI) in athletes, including concussion, is increasingly being found to have long-term sequelae. Current imaging techniques have not been able to identify early damage caused by mTBI that is predictive of long-term symptoms or chronic traumatic encephalopathy. In this preliminary feasibility study, the authors investigated the use of an emerging magnetic resonance imaging (MRI) technique, multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT), in visualizing acute and chronic white matter changes after mTBI in collegiate football and rugby players...
May 1, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29707601/an-assay-that-predicts-in-vivo-efficacy-for-dna-aptamers-that-stimulate-remyelination-in-a-mouse-model-of-multiple-sclerosis
#15
Robin M Heider, John A Smestad, Hernan Nicolas Lemus, Brandon Wilbanks, Arthur E Warrington, Justin P Peters, Moses Rodriguez, L James Maher
Multiple sclerosis (MS) is a debilitating disease for which regenerative therapies are sought. We have previously described human antibodies and DNA aptamer-streptavidin conjugates that promote remyelination after systemic injection into mice infected by Theiler's murine encephalomyelitis virus. Here, we report an in vitro assay of myelin binding with results that correlate with remyelination outcome in vivo , as shown for data from a set of DNA aptamer complexes of different size and formulation. This in vitro assay will be valuable for future screening of MS regenerative therapies targeting remyelination...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29706593/repurposing-hami3379-to-block-gpr17-and-promote-rodent-and-human-oligodendrocyte-differentiation
#16
Nicole Merten, Julia Fischer, Katharina Simon, Liguo Zhang, Ralf Schröder, Lucas Peters, Anne-Gaelle Letombe, Stephanie Hennen, Ramona Schrage, Theresa Bödefeld, Celine Vermeiren, Michel Gillard, Klaus Mohr, Qing Richard Lu, Oliver Brüstle, Jesus Gomeza, Evi Kostenis
Identification of additional uses for existing drugs is a hot topic in drug discovery and a viable alternative to de novo drug development. HAMI3379 is known as an antagonist of the cysteinyl-leukotriene CysLT2 receptor, and was initially developed to treat cardiovascular and inflammatory disorders. In our study we identified HAMI3379 as an antagonist of the orphan G protein-coupled receptor GPR17. HAMI3379 inhibits signaling of recombinant human, rat, and mouse GPR17 across various cellular backgrounds, and of endogenous GPR17 in primary rodent oligodendrocytes...
April 18, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29699382/transcriptional-profiling-of-mesenchymal-stem-cells-identifies-distinct-neuroimmune-pathways-altered-by-cns-disease
#17
Alex Sargent, Genevieve Shano, Molly Karl, Eric Garrison, Christian Miller, Robert H Miller
Background and Objectives: Bone marrow mesenchymal stem cells (BM-MSCs) are an attractive cell based therapy in the treatment of CNS demyelinating diseases such as multiple sclerosis (MS). Preclinical studies demonstrate that BM-MSCs can effectively reduce clinical burden and enhance recovery in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS. However, a number of recent clinical trials have not shown significant functional benefit following BM-MSC infusion into MS patients...
April 30, 2018: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29697861/microglial-mhc-class-ii-is-dispensable-for-experimental-autoimmune-encephalomyelitis-and-cuprizone-induced-demyelination
#18
Yochai Wolf, Anat Shemer, Liron Levy-Efrati, Mor Gross, Jung-Seok Kim, Adrien Engel, Eyal David, Louise Chappell-Maor, Jonathan Grozovski, Ron Rotkopf, Inbal Biton, Raya Eilam-Altstadter, Steffen Jung
Microglia are resident immune cells in the central nervous system (CNS), strategically positioned to clear dead cells and debris, and orchestrate CNS inflammation and immune defense. In steady state, these macrophages lack major histocompatibility complex class II (MHCII) expression, but microglia activation can be associated with MHCII induction. Whether microglial MHCII serves antigen presentation for critical local T cell re-stimulation in CNS auto-immune disorders or modulates microglial signaling output remains under debate...
April 26, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29695414/mtorc1-is-transiently-reactivated-in-injured-nerves-to-promote-c-jun-elevation-and-schwann-cell-dedifferentiation
#19
Camilla Norrmén, Gianluca Figlia, Patrick Pfistner, Jorge A Pereira, Sven Bachofner, Ueli Suter
Schwann cells (SCs) are endowed with a remarkable plasticity. When peripheral nerves are injured, SCs dedifferentiate and acquire new functions to coordinate nerve repair as so-called repair SCs. Subsequently, SCs redifferentiate to remyelinate regenerated axons. Given the similarities between SC de/redifferentiation in injured nerves and in demyelinating neuropathies, elucidating the signals involved in SC plasticity after nerve injury has potentially wider implications. c-Jun has emerged as a key transcription factor regulating SC dedifferentiation and the acquisition of repair SC features...
April 25, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29694345/diffusivity-in-the-core-of-chronic-multiple-sclerosis-lesions
#20
Alexander Klistorner, Chenyu Wang, Con Yiannikas, John Parratt, Joshua Barton, Yuyi You, Stuart L Graham, Michael H Barnett
BACKGROUND: Diffusion tensor imaging (DTI) has been suggested as a potential biomarker of disease progression, neurodegeneration and de/remyelination in MS. However, the pathological substrates that underpin alterations in brain diffusivity are not yet fully delineated. We propose that in highly cohesive fiber tracts: 1) a relative increase in parallel (axial) diffusivity (AD) may serve as a measure of increased extra-cellular space (ESC) within the core of chronic MS lesions and, as a result, may provide an estimate of the degree of tissue destruction, and 2) the contribution of the increased extra-cellular water to perpendicular (radial) diffusivity (RD) can be eliminated to provide a more accurate assessment of membranal (myelin) loss...
2018: PloS One
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