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Remyelination

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https://www.readbyqxmd.com/read/28436759/the-roles-of-micrornas-in-spinal-cord-injury
#1
Zhongju Shi, Hengxing Zhou, Lu Lu, Xueying Li, Zheng Fu, Jun Liu, Yi Kang, Zhijian Wei, Bin Pan, Lu Liu, Xiaohong Kong, Shiqing Feng
BACKGROUND AND PURPOSE: Spinal cord injury (SCI) involves serious damage that can result in abnormal or absent motor and sensory functions and a disruption of autonomic function, and a series of pathological reactions occur after the injury. As a type of small non-coding RNA, microRNAs (miRNAs) have been verified to inhibit gene expression via posttranscriptional regulation. This review mainly focuses on recent advances regarding the roles of miRNAs following SCI. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adopted...
April 24, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28428119/timing-of-high-efficacy-therapy-in-relapsing-remitting-multiple-sclerosis-a-systematic-review
#2
REVIEW
Bernd Merkel, Helmut Butzkueven, Anthony L Traboulsee, Eva Havrdova, Tomas Kalincik
BACKGROUND: Immunotherapy initiated early after first presentation of relapsing-remitting multiple sclerosis is associated with improved long-term outcomes. One can therefore speculate that early initiation of highly effective immunotherapies, with an average efficacy that is superior to the typical first-line therapies, could further improve relapse and disability outcomes. However, the most common treatment strategy is to commence first-line therapies, followed by treatment escalation in patients who continue to experience on-treatment disease activity...
April 17, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#3
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28409314/regulation-of-asymmetric-cell-division-in-mammalian-neural-stem-and-cancer-precursor-cells
#4
Mathieu Daynac, Claudia K Petritsch
Stem and progenitor cells are characterized by their abilities to self-renew and produce differentiated progeny. The balance between self-renewal and differentiation is achieved through control of cell division mode, which can be either asymmetric or symmetric. Failure to properly control cell division mode may result in premature depletion of the stem/progenitor cell pool or abnormal growth and impaired differentiation. In many tissues, including the brain, stem cells and progenitor cells undergo asymmetric cell division through the establishment of cell polarity...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28398505/cortical-remyelination-is-heterogeneous-in-multiple-sclerosis
#5
Eva M M Strijbis, Evert-Jan Kooi, Paul van der Valk, Jeroen J G Geurts
Cortical lesions (CLs) are an important component of multiple sclerosis (MS) pathology; they correlate better with physical disability and cognitive impairment than white matter lesions (WMLs). Because remyelination can be extensive in CLs, we quantified remyelination in gray matter (GM) and white matter (WM), addressing oligodendrocyte (OGD) maturation state and clinical relevance of remyelination. Brain tissue samples from 21 chronic MS patients were immunohistochemically stained for myelin proteolipid protein, Olig2, which is strongly expressed in OGD precursor cells (OPCs), but weakly expressed in mature OGDs and other OGD markers...
April 7, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28392360/matrine-promotes-nt3-expression-in-cns-cells-in-experimental-autoimmune-encephalomyelitis
#6
Ming-Liang Zhang, Xiao-Jian Zhang, Jian Kang, Hui-Jun Zhang, Xiao-Long Chen, Nan Liu, Shu-Qing Liu, Wen-Di Ma, Guang-Xian Zhang, Lin Zhu
Neurotrophin 3 (NT3) is a potent neurotrophic factor for promoting remyelination and recovery of neuronal function; upregulation of its expression in the central nervous system (CNS) is thus of major therapeutic importance for neurological deficits. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flavescent, has been recently reported to effectively ameliorate clinical signs in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by secreting antiinflammatory cytokines...
April 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28391986/gene-products-promoting-remyelination-are-up-regulated-in-a-cell-therapy-product-manufactured-from-banked-human-cord-blood
#7
Paula Scotland, Susan Buntz, Pamela Noeldner, Arjun Saha, Tracy Gentry, Joanne Kurtzberg, Andrew E Balber
BACKGROUND AIMS: DUOC-01, a cell product being developed to treat demyelinating conditions, is composed of macrophages that arise from CD14(+) monocytes in the mononuclear cell (MNC) population of banked cord blood (CB). This article demonstrates that expression of multiple gene products that promote remyelination is rapidly up-regulated during manufacturing of DUOC-01 from either MNC or purified CB CD14(+) monocytes. METHODS: Cell cultures were initiated with MNC or with immunoselected CD14(+) monocytes isolated from the same CB unit...
April 5, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28387380/a-staged-screening-of-registered-drugs-highlights-remyelinating-drug-candidates-for-clinical-trials
#8
C Eleuteri, S Olla, C Veroni, R Umeton, R Mechelli, S Romano, M C Buscarinu, F Ferrari, G Calò, G Ristori, M Salvetti, C Agresti
There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385597/ester-to-amide-rearrangement-of-ethanolamine-derived-prodrugs-of-sobetirome-with-increased-blood-brain-barrier-penetration
#9
Skylar J Ferrara, J Matthew Meinig, Andrew T Placzek, Tapasree Banerji, Peter McTigue, Meredith D Hartley, Hannah S Sanford-Crane, Tania Banerji, Dennis Bourdette, Thomas S Scanlan
Current therapeutic options for treating demyelinating disorders such as multiple sclerosis (MS) do not stimulate myelin repair, thus creating a clinical need for therapeutic agents that address axonal remyelination. Thyroid hormone is known to play an important role in promoting developmental myelination and repair, and CNS permeable thyromimetic agents could offer an increased therapeutic index compared to endogenous thyroid hormone. Sobetirome is a clinical stage thyromimetic that has been shown to have promising activity in preclinical models related to MS and X-linked adrenoleukodystrophy (X-ALD), a genetic disease that involves demyelination...
May 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28384535/effects-of-abstinence-and-chronic-cigarette-smoking-on-white-matter-microstructure-in-alcohol-dependence-diffusion-tensor-imaging-at-4t
#10
Yukai Zou, Donna E Murray, Timothy C Durazzo, Thomas P Schmidt, Troy A Murray, Dieter J Meyerhoff
BACKGROUND: We previously reported widespread microstructural deficits of brain white matter in alcohol-dependent individuals (ALC) compared to light drinkers in a small 1.5T diffusion tensor imaging study employing tract-based spatial statistics. Using a larger dataset acquired at 4T, the present study is an extension that investigated the effects of alcohol consumption, abstinence from alcohol, and comorbid cigarette smoking on white matter microstructure. METHODS: Tract-based spatial statistics were performed on 20 1-week-abstinent ALC, 52 1-month-abstinent ALC, and 30 controls...
March 19, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28381594/nimodipine-fosters-remyelination-in-a-mouse-model-of-multiple-sclerosis-and-induces-microglia-specific-apoptosis
#11
Andrea Schampel, Oleg Volovitch, Tobias Koeniger, Claus-Jürgen Scholz, Stefanie Jörg, Ralf A Linker, Erhard Wischmeyer, Marie Wunsch, Johannes W Hell, Süleyman Ergün, Stefanie Kuerten
Despite continuous interest in multiple sclerosis (MS) research, there is still a lack of neuroprotective strategies, because the main focus has remained on modulating the immune response. Here we performed in-depth analysis of neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and in in vitro studies regarding the effect of the well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated clinical EAE and spinal cord degeneration and promoted remyelination...
April 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28363754/intrathecal-insulin-like-growth-factor-1-but-not-insulin-enhances-myelin-repair-in-young-and-aged-rats
#12
Martin Hlavica, Aro Delparente, Andrin Good, Nicolas Good, Patricia S Plattner, Maryam S Seyedsadr, Martin E Schwab, Dianne P Figlewicz, Benjamin V Ineichen
One main pathological hallmark of multiple sclerosis (MS) is demyelination. Novel therapies which enhance myelin repair are urgently needed. Insulin and insulin-like growth factor 1 (IGF-1) have strong functional relationships. Here, we addressed the potential capacity of IGF-1 and insulin to enhance remyelination in an animal demyelination model in vivo. We found that chronic intrathecal infusion of IGF-1 enhanced remyelination after lysolecithin-induced demyelination in the spinal cord of young and aged rats...
March 29, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28359049/improved-neural-regeneration-with-olfactory-ensheathing-cell-inoculated-plga-scaffolds-in-spinal-cord-injury-adult-rats
#13
Changxing Wang, Chenglong Sun, Zhiying Hu, Xue Huo, Yang Yang, Xuehong Liu, Benson O A Botchway, Henry Davies, Marong Fang
BACKGROUND/AIMS: Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI). This study investigated the potential for poly (lactic-co-glycolic acid) (PLGA) complex inoculated with olfactory ensheathing cells (OECs) to treat spinal cord injury in a rat model. METHODS: OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR) p75. The Basso, Beattie, and Bresnahan (BBB) score, together with an inclined plane (IP) test were used to detect functional recovery...
March 30, 2017: Neuro-Signals
https://www.readbyqxmd.com/read/28358726/local-delivery-of-thyroid-hormone-enhances-oligodendrogenesis-and-myelination-after-spinal-cord-injury
#14
Robert B Shultz, Zhicheng Wang, Jia Nong, Zhiling Zhang, Yinghui Zhong
OBJECTIVE: Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs...
March 30, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28356890/evaluation-and-optimization-of-in-silico-designed-sphingosine-1-phosphate-s1p-receptor-subtype-1-modulators-for-the-management-of-multiple-sclerosis
#15
Daphne H Gusman, Claire Shoemake
Multiple Sclerosis (MS) is a chronic autoimmune disorder affecting the Central Nervous System (CNS) through inflammation, demyelination and neurodegeneration. Sphingosine-1-phosphate receptor (S1PR1) modulators have been approved for the management of MS. Phosphorylated fingolimod mimics endogenous sphingosine-1-phosphate (S1P), a bioactive lipid that regulates remyelination and cell injury. Amiselimod was developed as a successor of fingolimod, with more specificity for S1PR1, and showed promising results until phase 2 clinical trials...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28351411/activation-of-fxr-pathway-does-not-alter-glial-cell-function
#16
Stefanie Albrecht, Ann-Katrin Fleck, Ina Kirchberg, Stephanie Hucke, Marie Liebmann, Luisa Klotz, Tanja Kuhlmann
BACKGROUND: The nuclear receptor farnesoid-X-receptor (FXR; NR1H4) is expressed not only in the liver, gut, kidney and adipose tissue but also in the immune cells. FXR has been shown to confer protection in several animal models of inflammation, including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). FXR agonists are currently tested in clinical trials for treatment of human metabolic diseases. The beneficial effect of FXR agonists in EAE suggests that FXR might represent a potential target in inflammatory-demyelinating CNS diseases, such as MS...
March 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28350989/mir-219-cooperates-with-mir-338-in-myelination-and-promotes-myelin-repair-in-the-cns
#17
Haibo Wang, Ana Lis Moyano, Zhangyan Ma, Yaqi Deng, Yifeng Lin, Chuntao Zhao, Liguo Zhang, Minqing Jiang, Xuelian He, Zhixing Ma, Fanghui Lu, Mei Xin, Wenhao Zhou, Sung Ok Yoon, Ernesto R Bongarzone, Q Richard Lu
A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28344151/enhancing-oligodendrocyte-differentiation-by-transient-transcription-activation-via-dna-nanoparticle-mediated-transfection
#18
Xiaowei Li, Stephany Y Tzeng, Camila Gadens Zamboni, Vassilis E Koliatsos, Guo-Li Ming, Jordan J Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation...
March 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28338622/phosphodiesterase-inhibitors-as-a-therapeutic-approach-to-neuroprotection-and-repair
#19
REVIEW
Eric P Knott, Mazen Assi, Sudheendra N R Rao, Mousumi Ghosh, Damien D Pearse
A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334918/adaptive-human-immunity-drives-remyelination-in-a-mouse-model-of-demyelination
#20
Mohamed El Behi, Charles Sanson, Corinne Bachelin, Léna Guillot-Noël, Jennifer Fransson, Bruno Stankoff, Elisabeth Maillart, Nadège Sarrazin, Vincent Guillemot, Hervé Abdi, Isabelle Cournu-Rebeix, Bertrand Fontaine, Violetta Zujovic
One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells...
April 1, 2017: Brain: a Journal of Neurology
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