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Remyelination

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https://www.readbyqxmd.com/read/29157392/multiple-sclerosis-mechanisms-of-disease-and-strategies-for-myelin-and-axonal-repair
#1
REVIEW
Hernan Nicolas Lemus, Arthur E Warrington, Moses Rodriguez
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system with a variety of presentations and unclear pathogenesis. Multiple sclerosis has been associated with the term autoimmunity as a surrogate for pathogenesis. Multiple sclerosis is an organ-specific disease with immune-mediated myelin destruction. Understanding the complex etiology of multiple sclerosis and the importance of axon integrity is critical for clinicians who treat the disease. This review discusses the immune and autoimmune aspects of multiple sclerosis based on the current published data and novel evidence of strategies that promote remyelination and protect axons...
February 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29150266/interleukin-35-and-hepatocyte-growth-factor-as-a-novel-combined-immune-gene-therapy-for-multiple-sclerosis-disease
#2
Samira Moghadam, Maryam Erfanmanesh, Abdolreza Esmaeilzadeh
An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29148104/neuregulin-1-promotes-remyelination-and-fosters-a-pro-regenerative-inflammatory-response-in-focal-demyelinating-lesions-of-the-spinal-cord
#3
Hardeep Kataria, Arsalan Alizadeh, Ghazaleh M Shahriary, Shekoofeh Saboktakin Rizi, Ryan Henrie, Kallivalappil T Santhosh, James A Thliveris, Soheila Karimi-Abdolrezaee
Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination...
November 17, 2017: Glia
https://www.readbyqxmd.com/read/29146953/achievements-and-obstacles-of-remyelinating-therapies-in-multiple-sclerosis
#4
REVIEW
Martin Stangel, Tanja Kuhlmann, Paul M Matthews, Trevor J Kilpatrick
Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials...
November 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29143164/upregulation-of-myelin-gene-expression-by-a-physically-modified-saline-via-phosphatidylinositol-3-kinase-mediated-activation-of-creb-implications-for-multiple-sclerosis
#5
Malabendu Jana, Supurna Ghosh, Kalipada Pahan
An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimulated the expression of myelin-specific genes and proteins (myelin basic protein, MBP; myelin oligodendrocyte glycoprotein, MOG and proteolipid protein, PLP) in primary mouse oligodendroglia and mixed glial cells...
November 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29142295/regenerating-cns-myelin-from-mechanisms-to-experimental-medicines
#6
REVIEW
Robin J M Franklin, Charles Ffrench-Constant
Although the core concept of remyelination - based on the activation, migration, proliferation and differentiation of CNS progenitors - has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination...
November 16, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29136549/the-spectrum-of-charcot-marie-tooth-disease-due-to-myelin-protein-zero-an-electrodiagnostic-nerve-ultrasound-and-histological-study
#7
Gian Maria Fabrizi, Stefano Tamburin, Tiziana Cavallaro, Ilaria Cabrini, Moreno Ferrarini, Federica Taioli, Francesca Magrinelli, Giampietro Zanette
OBJECTIVE: Nerve ultrasound (US) data on myelin protein zero (MPZ)-related Charcot-Marie-Tooth disease (CMT) are lacking. To offer a comprehensive perspective on MPZ-related CMTs, we combined nerve US with clinics, electrodiagnosis and histopathology. METHODS: We recruited 36 patients (12 MPZ mutations), and correlated nerve US to clinical, electrodiagnostic measures, and sural nerve biopsy. RESULTS: According to motor nerve conduction velocity (MNCV) criteria, nine patients were categorized as "demyelinating" CMT1B, 17 as "axonal" CMT2I/J, and 10 as dominant "intermediate" CMTDID...
October 20, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29132838/therapeutic-effects-of-diosgenin-in-experimental-autoimmune-encephalomyelitis
#8
Weili Liu, Mei Zhu, Zhongwang Yu, Dou Yin, Fengfeng Lu, Yingyan Pu, Chao Zhao, Cheng He, Li Cao
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. Currently, there is no drug available to cure this kind of disease. Diosgenin is a plant-derived steroid saponin. A previous study in our lab revealed that diosgenin can promote oligodendrocyte progenitor cell differentiation and accelerate remyelination. In the present study, we found that diosgenin dose-dependently alleviated the progression of experimental autoimmune encephalomyelitis with reduced central nervous system inflammation and demyelination...
October 31, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29123527/erythropoietin-increases-myelination-in-oligodendrocytes-gene-expression-profiling-reveals-early-induction-of-genes-involved-in-lipid-transport-and-metabolism
#9
Georgina Gyetvai, Trisha Hughes, Florence Wedmore, Cieron Roe, Lamia Heikal, Pietro Ghezzi, Manuela Mengozzi
Several studies have shown that erythropoietin (EPO) has neuroprotective or neuroreparative actions on diseases of the nervous system and that improves oligodendrocyte (OL) differentiation and myelination in vivo and in vitro. This study aims at investigating the early molecular mechanisms for the pro-myelinating action of EPO at the gene expression level. For this purpose, we used a differentiating OL precursor cell line, rat central glia-4 cells. Cells were differentiated or not, and then treated with EPO for 1 or 20 h...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29114585/the-influence-of-retinoic-acid-on-the-human-oligodendrocyte-precursor-cells-by-rna-sequencing
#10
Sun Young Kim, Eve E Kelland, Ji Hong Kim, Brett T Lund, Xiao Chang, Kai Wang, Leslie P Weiner
Retinoic acid (RA), a metabolite of vitamin A, has been found to influence regeneration in the adult central nervous system (CNS). There may be an effect of RA in the recovery/repair in multiple sclerosis (MS), an autoimmune and neurodegenerative disease of the CNS. We hypothesized that RA is a regulator of the further differentiation of oligodendrocyte precursor cells (OPCs) - cells key to the remyelination process in MS. We conducted studies utilizing RNA-sequencing in human embryonic stem cell (hESC)-derived neural stem cells (NSCs) and OPCs so as to understand the role of transcriptional regulators during transition from both ESCs to NSCs and NSCs to OPCs...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29110780/multiple-sclerosis-and-other-demyelinating-and-autoimmune-inflammatory-diseases-of-the-central-nervous-system
#11
Clara Matute-Blanch, Xavier Montalban, Manuel Comabella
Multiple sclerosis (MS) is characterized by a substantial degree of heterogeneity in relation to clinical manifestations, disease course, radiologic findings, histopathologic characteristics of brain lesions, and response to treatment. In this scenario, there is a strong need in MS for biomarkers that reliably capture these diverse aspects of disease heterogeneity and assist, for instance, in disease diagnosis and stratification, in the prediction of disease course, or in the identification of new and effective therapies for the disease...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29108879/remyelination-modulators-in-multiple-sclerosis-patients
#12
Rabeah Al-Temaimi, Jehad AbuBaker, Irina Al-Khairi, Raed Alroughani
Multiple Sclerosis (MS) is a complex autoimmune neuro-inflammatory disorder characterized by persistent MS plaques in the central nervous system. Resolution of MS plaques is dependent on the remyelination competence of surviving oligodendrocytes and surrounding environment. Here, we assessed myelination modulators in a 100 MS patients against 77 healthy controls. Plasma fractions were used for the assessment of insulin growth factor binding protein1 (IGFBP1), brain-derived neurotrophic factor (BDNF), and lipocalin2 (LCN2) using a Luminex multiplex assay, whereas neurofilament light chain (NF-L) was assessed with an enzyme-linked immunosorbent assay...
November 8, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29103804/fibrinogen-activates-bmp-signaling-in-oligodendrocyte-progenitor-cells-and-inhibits-remyelination-after-vascular-damage
#13
Mark A Petersen, Jae Kyu Ryu, Kae-Jiun Chang, Ainhoa Etxeberria, Sophia Bardehle, Andrew S Mendiola, Wanjiru Kamau-Devers, Stephen P J Fancy, Andrea Thor, Eric A Bushong, Bernat Baeza-Raja, Catriona A Syme, Michael D Wu, Pamela E Rios Coronado, Anke Meyer-Franke, Stephanie Yahn, Lauriane Pous, Jae K Lee, Christian Schachtrup, Hans Lassmann, Eric J Huang, May H Han, Martina Absinta, Daniel S Reich, Mark H Ellisman, David H Rowitch, Jonah R Chan, Katerina Akassoglou
Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro...
October 19, 2017: Neuron
https://www.readbyqxmd.com/read/29095924/distinct-ng2-proteoglycan-dependent-roles-of-resident-microglia-and-bone-marrow-derived-macrophages-during-myelin-damage-and-repair
#14
Karolina Kucharova, William B Stallcup
We used a bone marrow transplantation approach to distinguish the activities of bone marrow-derived macrophages from the activities of central nervous system-resident microglia in phenomena associated with axon demyelination and remyelination. We transplanted wild type or germline NG2 null beta-actin-EGFP expressing bone marrow into irradiated wild type or NG2 null recipient mice, followed by analysis of lysolecithin-induced spinal cord demyelination and remyelination and quantification of Iba-1+/ F4/80+/ EGFP+ macrophages and Iba-1+/ F4/80+/ EGFP- microglia...
2017: PloS One
https://www.readbyqxmd.com/read/29092800/in-vivo-imaging-of-mauthner-axon-regeneration-remyelination-and-synapses-re-establishment-after-laser-axotomy-in-zebrafish-larvae
#15
Bing-Bing Hu, Min Chen, Rong-Chen Huang, Yu-Bin Huang, Yang Xu, Wu Yin, Lei Li, Bing Hu
Zebrafish is an excellent model to study central nervous system (CNS) axonal degeneration and regeneration since we can observe these processes in vivo and in real time in transparent larvae. Previous studies have shown that Mauthner cell (M-cell) axon regenerates poorly after mechanical spinal cord injury. Inconsistent with this result, however, we have found that M-cell possesses a great capacity for axon regeneration after two-photon laser ablation. By using ZEISS LSM 710 two-photon microscope, we performed specific unilateral axotomy of GFP labeled M-cells in the Tol-056 enhancer trap line larvae...
October 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29078396/thin-myelin-sheaths-as-the-hallmark-of-remyelination-persist-over-time-and-preserve-axon-function
#16
Ian D Duncan, Rachel L Marik, Aimee T Broman, Moones Heidari
The presence of thin myelin sheaths in the adult CNS is recognized as a marker of remyelination, although the reason there is not a recovery from demyelination to normal myelin sheath thickness remains unknown. Remyelination is the default pathway after myelin loss in all mammalian species, in both naturally occurring and experimental disease. However, there remains uncertainty about whether these thin sheaths thicken with time and whether they remain viable for extended periods. We provide two lines of evidence here that thin myelin sheaths may persist indefinitely in long-lived animal models...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29076591/long-term-magnetization-transfer-ratio-evolution-in-multiple-sclerosis-white-matter-lesions
#17
Yufan Zheng, Jar-Chi Lee, Richard Rudick, Elizabeth Fisher
BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR), a magnetic resonance imaging technique used to assess tissue integrity, correlates with demyelination and axonal loss in multiple sclerosis (MS) lesions. In acute white matter lesions, short-term MTR changes mainly reflect demyelination and remyelination, in addition to edema and axonal and glial changes. Long-term MTR changes in MS lesions have not been studied extensively. METHODS: A new quantitative image analysis method was developed to measure long-term MTR changes in MS lesions...
October 27, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/29075188/high-yield-of-adult-oligodendrocyte-lineage-cells-obtained-from-meningeal-biopsy
#18
Sissi Dolci, Annachiara Pino, Valeria Berton, Pau Gonzalez, Alice Braga, Marta Fumagalli, Elisabetta Bonfanti, Giorgio Malpeli, Francesca Pari, Stefania Zorzin, Clelia Amoroso, Denny Moscon, Francisco J Rodriguez, Guido Fumagalli, Francesco Bifari, Ilaria Decimo
Oligodendrocyte loss can lead to cognitive and motor deficits. Current remyelinating therapeutic strategies imply either modulation of endogenous oligodendrocyte precursors or transplantation of in vitro expanded oligodendrocytes. Cell therapy, however, still lacks identification of an adequate source of oligodendrocyte present in adulthood and able to efficiently produce transplantable cells. Recently, a neural stem cell-like population has been identified in meninges. We developed a protocol to obtain high yield of oligodendrocyte lineage cells from one single biopsy of adult rat meningeal tissue...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29073528/microglia-origins-homeostasis-and-roles-in-myelin-repair
#19
REVIEW
Amy F Lloyd, Claire L Davies, Veronique E Miron
Microglia are the resident macrophages of the central nervous system (CNS), implicated in developmental processes, homeostasis, and responses to injury. Derived from the yolk sac during development, microglia self-renew, self-regulate their numbers during homeostatic conditions, and show a robust proliferative capacity even in adulthood. Together with monocyte-derived macrophages (MDM), microglia coordinate the regeneration of CNS myelin around axons, termed remyelination. Gene expression analyses and experimental modelling have identified pro-remyelination roles for microglia/MDM in clearance of myelin debris, secretion of growth factors, and remodelling of the extracellular matrix...
October 23, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29073203/dynamics-and-heterogeneity-of-brain-damage-in-multiple-sclerosis
#20
Ekaterina Kotelnikova, Narsis A Kiani, Elena Abad, Elena H Martinez-Lapiscina, Magi Andorra, Irati Zubizarreta, Irene Pulido-Valdeolivas, Inna Pertsovskaya, Leonidas G Alexopoulos, Tomas Olsson, Roland Martin, Friedemann Paul, Jesper Tegnér, Jordi Garcia-Ojalvo, Pablo Villoslada
Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination...
October 2017: PLoS Computational Biology
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