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Remyelination

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https://www.readbyqxmd.com/read/28315956/axonal-transport-deficits-in-multiple-sclerosis-spiraling-into-the-abyss
#1
REVIEW
Robert van den Berg, Casper C Hoogenraad, Rogier Q Hintzen
The transport of mitochondria and other cellular components along the axonal microtubule cytoskeleton plays an essential role in neuronal survival. Defects in this system have been linked to a large number of neurological disorders. In multiple sclerosis (MS) and associated models such as experimental autoimmune encephalomyelitis (EAE), alterations in axonal transport have been shown to exist before neurodegeneration occurs. Genome-wide association (GWA) studies have linked several motor proteins to MS susceptibility, while neuropathological studies have shown accumulations of proteins and organelles suggestive for transport deficits...
March 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#2
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28300134/white-matter-repair-after-extracellular-vesicles-administration-in-an-experimental-animal-model-of-subcortical-stroke
#3
Laura Otero-Ortega, Fernando Laso-García, María Del Carmen Gómez-de Frutos, Berta Rodríguez-Frutos, Jorge Pascual-Guerra, Blanca Fuentes, Exuperio Díez-Tejedor, María Gutiérrez-Fernández
Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50-100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296347/gdnf-schwann-cells-in-hydrogel-scaffolds-promote-regional-axon-regeneration-remyelination-and-functional-improvement-after-spinal-cord-transection-in-rats
#4
Bingkun K Chen, Nicolas N Madigan, Jeffrey S Hakim, Mahrokh Dadsetan, Siobhan S McMahon, Michael J Yaszemski, Anthony J Windebank
Positively-charged oligo[poly(ethylene glycol)fumarate] (OPF(+) ) is a biodegradable hydrogel used for spinal cord injury repair. We compared scaffolds containing primary Schwann cells (SCs) to scaffolds delivering SCs genetically modified to secrete high concentrations of glial cell-derived neurotrophic factor (GDNF). Multichannel OPF(+) scaffolds loaded with SCs or GDNF-SCs were implanted into transected rat spinal cords for 4 weeks. GDNF-SCs promoted regeneration of more axons into OPF(+) scaffolds (2773...
March 10, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28288125/regulatory-t-cells-promote-myelin-regeneration-in-the-central-nervous-system
#5
Yvonne Dombrowski, Thomas O'Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, George Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard Perbal, Anna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin, Denise C Fitzgerald
Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg...
March 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28283336/tissue-engineering-with-peripheral-blood-derived-mesenchymal-stem-cells-promotes-the-regeneration-of-injured-peripheral-nerves
#6
Mengjie Pan, Xianghai Wang, Yijing Chen, Shangtao Cao, Jinkun Wen, Guofeng Wu, Yuanyuan Li, Lixia Li, Changhui Qian, Zhenqi Qin, Zhenlin Li, Dandan Tan, Zhihao Fan, Wutian Wu, Jiasong Guo
Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP...
March 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28280460/androstenediol-reduces-demyelination-induced-axonopathy-in-the-rat-corpus-callosum-impact-on-microglial-polarization
#7
Samah Kalakh, Abdeslam Mouihate
Aims: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. Methods: A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28270745/chaperone-proteins-in-the-central-nervous-system-and-peripheral-nervous-system-after-nerve-injury
#8
REVIEW
Shalina S Ousman, Ariana Frederick, Erin-Mai F Lim
Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28269761/treatment-with-a-recombinant-human-igm-that-recognizes-psa-ncam-preserves-brain-pathology-in-mog-induced-experimental-autoimmune-encephalomyelitis
#9
Hernan Nicolas Lemus, Arthur E Warrington, Aleksandar Denic, Bharath Wootla, Moses Rodriguez
A single peripheral dose of CNS-binding IgMs promote remyelination and preserve axons in a number of animal models of neurologic disease. A myelin-binding recombinant human IgM (rHIgM22) is presently in a safety trial in MS patients following an acute MS exacerbation. rHIgM22 (directed against oligodendrocytes) or rHIgM12 (directed against neurons) were administered to mice with MOG-induced experimental autoimmune encephalomyelitis (EAE) with study endpoints: clinical deficits and brain and spinal cord pathology...
February 24, 2017: Human Antibodies
https://www.readbyqxmd.com/read/28262732/transplantation-of-huc-mscs-seeded-collagen-scaffolds-reduces-scar-formation-and-promotes-functional-recovery-in-canines-with-chronic-spinal-cord-injury
#10
Xing Li, Jun Tan, Zhifeng Xiao, Yannan Zhao, Sufang Han, Dingyang Liu, Wen Yin, Jing Li, Juan Li, Siyi Wanggou, Bing Chen, Caiping Ren, Xingjun Jiang, Jianwu Dai
Spinal cord injury (SCI) can lead to locomotor deficits, and the repair of chronic SCI is considered one of the most challenging clinical problems. Although extensive studies have evaluated treatments for acute SCI in small animals, comparatively fewer studies have been conducted on large-animal SCI in the chronic phase, which is more clinically relevant. Here, we used a collagen-based biomaterial, named the NeuroRegen scaffold, loaded with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a canine chronic SCI model...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261102/genetic-and-pharmacological-inhibition-of-p38%C3%AE-improves-locomotor-recovery-after-spinal-cord-injury
#11
Hiroki Umezawa, Yusuke Naito, Kensuke Tanaka, Kento Yoshioka, Kenichi Suzuki, Tatsuhiko Sudo, Masahiko Hagihara, Masahiko Hatano, Koichiro Tatsumi, Yoshitoshi Kasuya
One of the mitogen-activated protein kinases, p38α plays a crucial role in various inflammatory diseases and apoptosis of various types of cells. In this study, we investigated the pathophysiological roles of p38α in spinal cord injury (SCI), using a mouse model. Lateral hemisection at T9 of the SC was performed in wild type (WT) and p38α(+/-) mice (p38α(-/-) showed embryonic lethality). p38α(+/-) mice showed a better functional recovery from SCI-associated paralyzed hindlimbs compared to WT mice at 7 days post-injury (dpi), which remained until 28 dpi (an end time point of monitoring the behavior)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28256546/promoting-in-vivo-remyelination-with-small-molecules-a-neuroreparative-pharmacological-treatment-for-multiple-sclerosis
#12
Eva María Medina-Rodríguez, Ana Bribián, Amanda Boyd, Valle Palomo, Jesús Pastor, Alfonso Lagares, Carmen Gil, Ana Martínez, Anna Williams, Fernando de Castro
Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28253550/olig1-is-required-for-noggin-induced-neonatal-myelin-repair
#13
Jennifer K Sabo, Vivi Heine, John C Silbereis, Lucas Schirmer, Steven W Levison, David H Rowitch
Objective - Neonatal white matter injury (NWMI) is a lesion found in preterm infants that can lead to cerebral palsy. Although antagonists of bone morphogenetic protein (BMP) signaling, such as Noggin, promote oligodendrocyte precursor cell (OPC) production after hypoxic-ischemic injury, the downstream functional targets are poorly understood. The bHLH protein Olig1 promotes oligodendrocyte (OL) development and is essential during remyelination in adult mice. Here, we investigated whether Olig1 function is required downstream of BMP antagonism for the response to injury in the neonatal brain...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28251686/e6020-a-synthetic-tlr4-agonist-accelerates-myelin-debris-clearance-schwann-cell-infiltration-and-remyelination-in-the-rat-spinal-cord
#14
Jamie S Church, Lindsay M Milich, Jessica K Lerch, Phillip G Popovich, Dana M McTigue
Oligodendrocyte progenitor cells (OPCs) are present throughout the adult brain and spinal cord and can replace oligodendrocytes lost to injury, aging, or disease. Their differentiation, however, is inhibited by myelin debris, making clearance of this debris an important step for cellular repair following demyelination. In models of peripheral nerve injury, TLR4 activation by lipopolysaccharide (LPS) promotes macrophage phagocytosis of debris. Here we tested whether the novel synthetic TLR4 agonist E6020, a Lipid A mimetic, promotes myelin debris clearance and remyelination in spinal cord white matter following lysolecithin-induced demyelination...
March 2, 2017: Glia
https://www.readbyqxmd.com/read/28251676/the-balance-between-cathepsin-c-and-cystatin-f-controls-remyelination-in-the-brain-of-plp1-overexpressing-mouse-a-chronic-demyelinating-disease-model
#15
Takahiro Shimizu, Wilaiwan Wisessmith, Jiayi Li, Manabu Abe, Kenji Sakimura, Banthit Chetsawang, Yoshinori Sahara, Koujiro Tohyama, Kenji F Tanaka, Kazuhiro Ikenaka
In demyelinating diseases such as multiple sclerosis (MS), an imbalance between the demyelination and remyelination rates underlies the degenerative processes. Microglial activation is observed in demyelinating lesions; however, the molecular mechanism responsible for the homeostatic/environmental change remains elusive. We previously found that cystatin F (CysF), a cysteine protease inhibitor, is selectively expressed in microglia only in actively demyelinating/remyelinating lesions but ceases expression in chronic lesions, suggesting its role in remyelination...
March 2, 2017: Glia
https://www.readbyqxmd.com/read/28250735/glial-kon-ng2-gene-network-for-central-nervous-system-repair
#16
REVIEW
Maria Losada-Perez, Neale Harrison, Alicia Hidalgo
The glial regenerative response to central nervous system (CNS) injury, although limited, can be harnessed to promote regeneration and repair. Injury provokes the proliferation of ensheathing glial cells, which can differentiate to remyelinate axons, and partially restore function. This response is evolutionarily conserved, strongly implying an underlying genetic mechanism. In mammals, it is elicited by NG2 glia, but most often newly generated cells fail to differentiate. Thus an important goal had been to find out how to promote glial differentiation following the proliferative response...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28250011/microglia-driven-regulation-of-oligodendrocyte-lineage-cells-myelination-and-remyelination
#17
REVIEW
Veronique E Miron
Microglia are the resident macrophages of the CNS and members of the innate immune system. As such, they serve important functions in surveillance for indicators of damage and subsequent initiation of an inflammatory response. Although often implicated in neural damage, recent studies have also suggested beneficial roles of activated microglia and inflammation in developmental and regenerative processes in the CNS. These include regulating events leading to the generation and regeneration of myelin, the insulation surrounding nerve fibers which is critical for nerve health and function...
March 1, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28237816/mir-146a-promotes-remyelination-in-a-cuprizone-model-of-demyelinating-injury
#18
Jing Zhang, Zheng Gang Zhang, Mei Lu, Xinli Wang, Xia Shang, Stanton B Elias, Michael Chopp
The death of mature oligodendrocytes (OLs) which are the sole myelinating cells of the central nervous system (CNS), leads to demyelination and functional deficits. Currently, there is lack of effective remyelination therapies for patients with demyelinating diseases. MicroRNAs (miRNAs) mediate OL function. We hypothesized that miR-146a, by inactivating interleukin-1 receptor-associated kinase 1 (IRAK1), promotes differentiation of oligodendrocyte progenitor cells (OPCs) and thereby enhances remyelination. To test this hypothesis, a demyelination model induced by a cuprizone (CPZ) diet was employed, in which C57BL/6J mice were fed with a CPZ diet for 5weeks...
February 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28229892/safety-and-efficacy-of-opicinumab-in-acute-optic-neuritis-renew-a-randomised-placebo-controlled-phase-2-trial
#19
Diego Cadavid, Laura Balcer, Steven Galetta, Orhan Aktas, Tjalf Ziemssen, Ludo Vanopdenbosch, Jette Frederiksen, Mark Skeen, Glenn J Jaffe, Helmut Butzkueven, Focke Ziemssen, Luca Massacesi, Yi Chai, Lei Xu, Stefanie Freeman
BACKGROUND: The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We therefore assessed the safety and tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode. METHODS: This randomised, double-blind, placebo-controlled, phase 2 study (RENEW) was done at 33 sites in Australia, Canada, and Europe in participants (aged 18-55 years) with a first unilateral acute optic neuritis episode within 28 days from study baseline...
March 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28224237/attempts-to-overcome-remyelination-failure-toward-opening-new-therapeutic-avenues-for-multiple-sclerosis
#20
REVIEW
Mahsa Motavaf, Majid Sadeghizadeh, Mohammad Javan
Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath wrapped around the axons and eventual axon degeneration. The disease is pathologically heterogeneous; however, perhaps its most frustrating aspect is the lack of efficient regenerative response for remyelination. Current treatment strategies are based on anti-inflammatory or immunomodulatory medications that have the potential to reduce the numbers of newly evolving lesions...
February 21, 2017: Cellular and Molecular Neurobiology
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