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Myelin repair

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https://www.readbyqxmd.com/read/28229330/the-involvement-of-the-myelin-associated-inhibitors-and-their-receptors-in-cns-plasticity-and-injury
#1
REVIEW
Anthony G Boghdadi, Leon Teo, James A Bourne
The limited capacity for the central nervous system (CNS) to repair itself was first described over 100 years ago by Spanish neuroscientist Ramon Y. Cajal. However, the exact mechanisms underlying this failure in neuronal regeneration remain unclear and, as such, no effective therapeutics yet exist. Numerous studies have attempted to elucidate the biochemical and molecular mechanisms that inhibit neuronal repair with increasing evidence suggesting that several inhibitory factors and repulsive guidance cues active during development actually persist into adulthood and may be contributing to the inhibition of repair...
February 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28224637/compound-motor-action-potential-duration-and-latency-are-markers-of-recurrent-laryngeal-nerve-injury
#2
Neel K Bhatt, Andrea M Park, Mohammad T Al-Lozi, Derrick C Gale, Randal C Paniello
OBJECTIVE: Compound motor action potential (CMAP) can quantitatively evaluate innervation following injury to the recurrent laryngeal nerve (RLN) in canines. CMAP duration (the total time of CMAP) and latency (the time between the nerve impulse and the onset of action potentials) have not been assessed following RLN injury. STUDY DESIGN: Animal study. METHODS: Twelve canine hemilaryngeal preparations were investigated. Baseline CMAP duration and latency were derived...
February 22, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28224237/attempts-to-overcome-remyelination-failure-toward-opening-new-therapeutic-avenues-for-multiple-sclerosis
#3
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
https://www.readbyqxmd.com/read/28203609/zeb2-inhibiting-the-inhibitors-in-schwann-cells
#4
Bastian G Brinkmann, Susanne Quintes
Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28191764/neural-progenitor-like-cells-induced-from-human-gingiva-derived-mesenchymal-stem-cells-regulate-myelination-of-schwann-cells-in-rat-sciatic-nerve-regeneration
#5
Qunzhou Zhang, Phuong Nguyen, Qilin Xu, Wonse Park, Sumin Lee, Akihiro Furuhashi, Anh D Le
Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191668/inflammatory-demyelination-induces-ependymal-modifications-concomitant-to-activation-of-adult-svz-stem-cell-proliferation
#6
Fereshteh Pourabdolhossein, Sara Gil-Perotín, Paula Garcia-Belda, Aurelien Dauphin, Sabah Mozafari, Vanja Tepavcevic, Jose Manuel Garcia Verdugo, Anne Baron-Van Evercooren
Ependymal cells (E1/E2) and ciliated B1cells confer a unique pinwheel architecture to the ventricular surface of the subventricular zone (SVZ), and their cilia act as sensors to ventricular changes during development and aging. While several studies showed that forebrain demyelination reactivates the SVZ triggering proliferation, ectopic migration, and oligodendrogenesis for myelin repair, the potential role of ciliated cells in this process was not investigated. Using conventional and lateral wall whole mount preparation immunohistochemistry in addition to electron microscopy in a forebrain-targeted model of experimental autoimmune encephalomyelitis (tEAE), we show an early decrease in numbers of pinwheels, B1 cells, and E2 cells...
February 13, 2017: Glia
https://www.readbyqxmd.com/read/28186702/direct-conversion-of-human-fibroblasts-into-schwann-cells-that-facilitate-regeneration-of-injured-peripheral-nerve-in-vivo
#7
Yoshihiro Sowa, Tsunao Kishida, Koichi Tomita, Kenta Yamamoto, Toshiaki Numajiri, Osam Mazda
Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs)...
January 9, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28182653/protecting-cells-by-protecting-their-vulnerable-lysosomes-identification-of-a-new-mechanism-for-preserving-lysosomal-functional-integrity-upon-oxidative-stress
#8
Raquel Pascua-Maestro, Sergio Diez-Hermano, Concepción Lillo, Maria D Ganfornina, Diego Sanchez
Environmental insults such as oxidative stress can damage cell membranes. Lysosomes are particularly sensitive to membrane permeabilization since their function depends on intraluminal acidic pH and requires stable membrane-dependent proton gradients. Among the catalog of oxidative stress-responsive genes is the Lipocalin Apolipoprotein D (ApoD), an extracellular lipid binding protein endowed with antioxidant capacity. Within the nervous system, cell types in the defense frontline, such as astrocytes, secrete ApoD to help neurons cope with the challenge...
February 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28176458/serum-free-bioprocessing-of-adult-human-and-rodent-skin-derived-schwann-cells-implications-for-cell-therapy-in-nervous-system-injury
#9
Leila Mirfeizi, Jo Anne Stratton, Ranjan Kumar, Prajay Shah, Natacha Agabalyan, Morgan G Stykel, Rajiv Midha, Jeff Biernaskie, Michael S Kallos
Peripheral nerve injury affects 2.8% of trauma patients with severe cases often resulting in long-lived permanent disability, despite nerve repair surgery. Autologous Schwann cell (SC) therapy currently provides an exciting avenue for improved outcomes for these patients, particularly with the possibility to derive SCs from easily-accessible adult skin. However, due to current challenges regarding the efficient expansion of these cells, further optimization is required before they can be seriously considered for clinical application...
February 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28169834/development-of-biomimetic-micro-patterned-device-incorporated-with-neurotrophic-gradient-and-supportive-schwann-cells-for-the-applications-in-neural-tissue-engineering
#10
Chia-Wei Yeh, Li-Wen Wang, Hsi-Chin Wu, Yi-Kong Hsieh, Jane Wang, Ming-Hong Chen, Tzu-Wei Wang
In these years, the artificial nerve guidance conduit has been developed as an alternative way to repair peripheral nerve injury. Unlike autologous nerve graft, the artificial nerve guidance conduit without proper stimulating factors and guidance cues still cannot obtain satisfactory prognosis for clinical patients. In this study, a biodegradable polymer-based implantable device has been developed and characterized. By incorporating three stimulating factors: 1) micro-patterned surface that can directionally guide the axon as physical cue; 2) neurotrophic gradient membrane that can continually attract axon outgrowth from the proximal to distal stump as chemical cue; 3) Schwann cells that can support the growth of neurite and form myelin sheath around axon as biological cue, we expect that this construct can be used as a promising nerve guidance conduit for peripheral nerve regeneration...
February 7, 2017: Biofabrication
https://www.readbyqxmd.com/read/28161197/icariin-enhances-remyelination-process-after-acute-demyelination-induced-by-cuprizone-exposure
#11
Yifan Zhang, Linlin Yin, Na Zheng, Li Zhang, Jianghong Liu, Weixiong Liang, Qi Wang
Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal...
February 1, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28147220/intersections-of-pathways-involving-biotin-and-iron-relative-to-therapeutic-mechanisms-for-progressive-multiple-sclerosis
#12
Rebecca M Heidker, Mitchell R Emerson, Steven M LeVine
While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28145507/transplanted-mir-219-overexpressing-oligodendrocyte-precursor-cells-promoted-remyelination-and-improved-functional-recovery-in-a-chronic-demyelinated-model
#13
Hong-Bin Fan, Li-Xia Chen, Xue-Bin Qu, Chuan-Lu Ren, Xiu-Xiang Wu, Fu-Xing Dong, Bao-Le Zhang, Dian-Shuai Gao, Rui-Qin Yao
Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28144983/human-olfactory-mesenchymal-stromal-cell-transplants-promote-remyelination-and-earlier-improvement-in-gait-co-ordination-after-spinal-cord-injury
#14
Susan L Lindsay, Andrew Toft, Jacob Griffin, Ahmed M M Emraja, Susan Carol Barnett, John S Riddell
Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals. In addition to the typical distribution in the dorsal columns (common to all animals), in transplanted animals only, P0 immunolabelling was consistently detected in white matter lateral and ventral to the injury site...
February 1, 2017: Glia
https://www.readbyqxmd.com/read/28139851/betacellulin-regulates-schwann-cell-proliferation-and-myelin-formation-in-the-injured-mouse-peripheral-nerve
#15
Nicolas Vallières, Benoit Barrette, Linda Xiang Wang, Erik Bélanger, Louise Thiry, Marlon R Schneider, Mohammed Filali, Daniel Côté, Frédéric Bretzner, Steve Lacroix
When a nerve fiber is cut or crushed, the axon segment that is separated from the soma degenerates distal from the injury in a process termed Wallerian degeneration (WD). C57BL/6OlaHsd-Wld(S) (Wld(S) ) mutant mice exhibit significant delays in WD. This results in considerably delayed Schwann cell and macrophage responses and thus in impaired nerve regenerations. In our previous work, thousands of genes were screened by DNA microarrays and over 700 transcripts were found to be differentially expressed in the injured sciatic nerve of Wld(S) compared with wild-type (WT) mice...
January 31, 2017: Glia
https://www.readbyqxmd.com/read/28139683/delaying-histone-deacetylase-response-to-injury-accelerates-conversion-into-repair-schwann-cells-and-nerve-regeneration
#16
Valérie Brügger, Mert Duman, Maëlle Bochud, Emmanuelle Münger, Manfred Heller, Sophie Ruff, Claire Jacob
The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development...
January 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28127945/in-vivo-conversion-of-astrocytes-to-myelinating-cells-by-mir-302-367-and-valproate-to-enhance-myelin-repair
#17
Maryam Ghasemi-Kasman, Leila Zare, Hossein Baharvand, Mohammad Javan
Enhancement of repair potential for degenerative brain diseases has been a research priority during recent years. Considering recent advancements in the field of direct transdifferentiation, conversion of astrocytes as a prominent component of glial scars to the progenitor cells that contribute to the repair mechanisms seems interesting. Recently, we have reported miR-302/367-mediated in vivo conversion of astrocytes into neuroblasts and neurons. In the current study, we used miR-302/367 and valproate (VPA) to show the possibility of conversion of astrocytes to oligodendrocyte progenitor cells and myelinating cells in a cuprizone (CPZ)-induced model of demyelination...
January 27, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28124770/the-effect-of-stereotactic-injections-on-demyelination-and-remyelination-a-study-in-the-cuprizone-model
#18
Laura Salinas Tejedor, Tanja Wostradowski, Stefan Gingele, Thomas Skripuletz, Viktoria Gudi, Martin Stangel
Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination...
January 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28117328/dietary-cholesterol-promotes-repair-of-demyelinated-lesions-in-the-adult-brain
#19
Stefan A Berghoff, Nina Gerndt, Jan Winchenbach, Sina K Stumpf, Leon Hosang, Francesca Odoardi, Torben Ruhwedel, Carolin Böhler, Benoit Barrette, Ruth Stassart, David Liebetanz, Payam Dibaj, Wiebke Möbius, Julia M Edgar, Gesine Saher
Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol...
January 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28107629/discovery-of-1-2-3-triazole-derivatives-for-multimodality-pet-ct-cryoimaging-of-myelination-in-the-central-nervous-system
#20
Chunying Wu, Brendan Eck, Sheng Zhang, Junqing Zhu, Anand Dev Tiwari, Yifan Zhang, Yunjie Zhu, Jinming Zhang, Bin Wang, Xizhen Wang, Xu Wang, Jingqiang You, Jian Wang, Yihui Guan, Xingdang Liu, Xin Yu, Bruce D Trapp, Robert Miller, Jerry Silver, David Wilson, Yanming Wang
Myelin pathology is present in many neurological conditions such as multiple sclerosis (MS) and traumatic spinal cord injury (SCI). To facilitate development of novel therapies aimed at myelin repair, we set out to develop imaging agents that permit direct quantification of myelination in vivo. In this work, we designed and synthesized a series of fluorescent fluorinated myelin imaging agents that can be used for in vivo positron emission tomography (PET) imaging combined with subsequent post-mortem fluorescent cryoimaging...
February 9, 2017: Journal of Medicinal Chemistry
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