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Myelin repair

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https://www.readbyqxmd.com/read/28334918/adaptive-human-immunity-drives-remyelination-in-a-mouse-model-of-demyelination
#1
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...
February 22, 2017: Brain: a Journal of Neurology
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
#2
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/28293514/platysma-motor-nerve-transfer-for-restoring-marginal-mandibular-nerve-function
#3
Andres Rodriguez-Lorenzo, David Jensson, Wolfgang J Weninger, Melanie Schmid, Stefan Meng, Chieh-Han John Tzou
BACKGROUND: Injuries of the marginal mandibular nerve (MMN) of the facial nerve result in paralysis of the lower lip muscle depressors and an asymmetrical smile. Nerve reconstruction, when possible, is the method of choice; however, in cases of long nerve gaps or delayed nerve reconstruction, conventional nerve repairs may be difficult to perform or may provide suboptimal outcomes. Herein, we investigate the anatomical technical feasibility of transfer of the platysma motor nerve (PMN) to the MMN for restoration of lower lip function, and we present a clinical case where this nerve transfer was successfully performed...
December 2016: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28283336/tissue-engineering-with-peripheral-blood-derived-mesenchymal-stem-cells-promotes-the-regeneration-of-injured-peripheral-nerves
#4
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/28265351/elevated-axonal-membrane-permeability-and-its-correlation-with-motor-deficits-in-an-animal-model-of-multiple-sclerosis
#5
Gary Leung, Melissa Tully, Jonathan Tang, Shengxi Wu, Riyi Shi
BACKGROUND: It is increasingly clear that in addition to myelin disruption, axonal degeneration may also represent a key pathology in multiple sclerosis (MS). Hence, elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology, but also elucidate additional therapeutic targets. The objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE mice. METHODS: Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud's adjuvant emulsion, followed by two intraperitoneal injections of pertussis toxin...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28261764/a-biological-tube-technique-for-the-repair-of-peripheral-nerve-defects-using-stuffed-nerves
#6
Sercan Çapkın, Mustafa Akhisaroğlu, Bekir Uğur Ergür, Ali Abdülkadir Bacakoğlu
BACKGROUND: Presently described is research examining the "stuffed nerve" technique to repair peripheral nerve defects. METHODS: Twenty-one male Wistar Albino rats were divided into 3 groups of 7, and standard 10-mm defects were created in the sciatic nerve of all subjects. Rats were treated with autogenous nerve graft (Group 1), hollow vein graft (Group 2), or vein graft stuffed with shredded nerves (Group 3). After 12 weeks, electrophysiological and histomorphological analyses were performed to evaluate axonal regeneration...
January 2017: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/28261057/molecular-mechanisms-involved-in-schwann-cell-plasticity
#7
REVIEW
Angélique Boerboom, Valérie Dion, Alain Chariot, Rachelle Franzen
Schwann cell incredible plasticity is a hallmark of the utmost importance following nerve damage or in demyelinating neuropathies. After injury, Schwann cells undergo dedifferentiation before redifferentiating to promote nerve regeneration and complete functional recovery. This review updates and discusses the molecular mechanisms involved in the negative regulation of myelination as well as in the reprogramming of Schwann cells taking place early following nerve lesion to support repair. Significant advance has been made on signaling pathways and molecular components that regulate SC regenerative properties...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28253550/olig1-is-required-for-noggin-induced-neonatal-myelin-repair
#8
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
#9
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/28250760/transfer-of-the-extensor-indicis-proprius-branch-of-posterior-interosseous-nerve-to-reconstruct-ulnar-nerve-and-median-nerve-injured-proximally-an-anatomical-study
#10
Pei-Ji Wang, Yong Zhang, Jia-Ju Zhao, Ju-Pu Zhou, Zhi-Cheng Zuo, Bing-Bing Wu
Proximal or middle lesions of the ulnar or median nerves are responsible for extensive loss of hand motor function. This occurs even when the most meticulous microsurgical techniques or nerve grafts are used. Previous studies had proposed that nerve transfer was more effective than nerve grafting for nerve repair. Our hypothesis is that transfer of the posterior interosseous nerve, which contains mainly motor fibers, to the ulnar or median nerve can innervate the intrinsic muscles of hands. The present study sought to investigate the feasibility of reconstruction of the deep branch of the ulnar nerve and the thenar branch of median nerve by transferring the extensor indicis proprius branch of the posterior interosseous nerve obtained from adult cadavers...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28229330/the-involvement-of-the-myelin-associated-inhibitors-and-their-receptors-in-cns-plasticity-and-injury
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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 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
#19
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
#20
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 (NGC) has been developed as an alternative way to repair peripheral nerve injury. Unlike autologous nerve graft, the artificial NGC 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 (SCs) 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 NGC for peripheral nerve regeneration...
February 28, 2017: Biofabrication
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