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Myelin repair

Ryan Hamilton, Michael Walsh, Rashmi Singh, Karl Rodriguez, Xiaoli Gao, Md Mizanur Rahman, Asish Chaudhuri, Arunabh Bhattacharya
Aging is associated with a decline in peripheral nerve function of both motor and sensory nerves. The decline in function of peripheral sensorimotor nerves with aging has been linked to sarcopenia, the age-related decline in muscle mass and function that significantly compromises the quality of life in older humans. In this study, we report a significant increase in oxidized fatty acids and insoluble protein carbonyls in sciatic nerves of aged C57BL/6 male mice (28-30mo) that exhibit a profound decline in motor nerve function and degenerative changes in both axon and myelin structure, compared to young mice (6-8mo)...
November 15, 2016: Journal of the Neurological Sciences
Johanna Flygt, Fredrik Clausen, Niklas Marklund
BACKGROUND: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI...
October 17, 2016: Restorative Neurology and Neuroscience
Daniel Haselbach, Wassim Raffoul, Lorenz Larcher, Mathias Tremp, Daniel F Kalbermatten, Pietro G di Summa
INTRODUCTION: Hindlimb autophagy is common after rat sciatic total axotomy and is considered as a sign of neuropathic pain. We applied adult stem cells in a fibrin conduit in a total sciatic axotomy model to improve nerve regeneration, investigating whether a correlation could be detected between stem cells effects on regeneration and limb autophagy. MATERIAL AND METHODS: After sciatic nerve section, a 1-cm sciatic gap was crossed using fibrin conduits. EXPERIMENTAL: groups included empty fibrin conduits, fibrin conduits seeded with primary Schwann cells, and fibrin conduits seeded with Schwann cell-like differentiated mesenchymal or adipose-derived stem cells (dMSCs and dASCs)...
October 16, 2016: Neuroscience Letters
Mehmet Emin Önger, Burcu Delibaş, Aysın Pınar Türkmen, Erkan Erener, Berrin Zuhal Altunkaynak, Süleyman Kaplan
Nerve injuries result in functional loss in the innervated organ or body parts, and recovery is difficult unless surgical treatment has been done. Different surgical treatments have been suggested for nerve repair. Tissue engineering related to growth factors has arisen as an alternative approach for triggering and improving nerve regeneration. Therefore, the aim of this review is to provide a comprehensive analysis related to growth factors as tools for optimizing the regeneration process. Studies and reviews on the use of growth factors for nerve regeneration were compiled over the course of the review...
October 17, 2016: Drug Discoveries & Therapeutics
Jacob Kjell, Lars Olson
A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors...
October 1, 2016: Disease Models & Mechanisms
Matías Alvarez-Saavedra, Yves De Repentigny, Doo Yang, Ryan W O'Meara, Keqin Yan, Lukas E Hashem, Lemuel Racacho, Ilya Ioshikhes, Dennis E Bulman, Robin J Parks, Rashmi Kothary, David J Picketts
Exercise has been argued to enhance cognitive function and slow progressive neurodegenerative disease. Although exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects remain poorly understood. Conditional ablation of the Snf2h gene impairs cerebellar development producing mice with poor motor function, progressive ataxia, and death between postnatal days 25-45...
October 11, 2016: Cell Reports
Jaime Eugenín-von Bernhardi, Leda Dimou
NG2-glia are a mysterious and ubiquitous glial population with a highly branched morphology. Initial studies suggested that their unique function is the generation and maintenance of oligodendrocytes in the central nervous system (CNS), important for proper myelination and therefore for axonal support and fast conduction velocity. Over the last years this simplistic notion has been dramatically changed: the wide and homogeneous distribution of NG2-glia within all areas of the developing CNS that is maintained during the whole lifespan, their potential to also differentiate into other cell types in a spatiotemporal manner, their active capability of maintaining their population and their dynamic behavior in altered conditions have raised the question: are NG2-glia simple progenitor cells or do they play further major roles in the normal function of the CNS? In this chapter, we will discuss some important features of NG2-glia like their homeostatic distribution in the CNS and their potential to differentiate into diverse cell types...
2016: Advances in Experimental Medicine and Biology
Michael S Fleming, Jian J Li, Daniel Ramos, Tong Li, David A Talmage, Shin-Ichi Abe, Silvia Arber, Wenqin Luo
: Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET(+) mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Andrew T Placzek, Skylar J Ferrara, Meredith D Hartley, Hannah S Sanford-Crane, J Matthew Meinig, Thomas S Scanlan
There is currently great interest in developing drugs that stimulate myelin repair for use in demyelinating diseases such as multiple sclerosis. Thyroid hormone plays a key role in stimulating myelination during development and also controls the expression of important genes involved in myelin repair in adults. Because endogenous thyroid hormone in excess lacks a generally useful therapeutic index, it is not used clinically for indications other than hormone replacement; however, selective thyromimetics such as sobetirome offer a therapeutic alternative...
September 16, 2016: Bioorganic & Medicinal Chemistry
Davide Lecca, Davide Marangon, Giusy T Coppolino, Aida Menéndez Méndez, Annamaria Finardi, Gloria Dalla Costa, Vittorio Martinelli, Roberto Furlan, Maria P Abbracchio
In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS)...
October 4, 2016: Scientific Reports
Pedro Hernández-Cortés, Miguel Angel Toledo-Romero, Mario Delgado, Elena Gonzalez-Rey, Rafael Gómez Sánchez, Nicolás Prados, José Aneiros-Fernández, Vicente Crespo-Lora, Mariano Aguilar, Pablo Galindo-Moreno, Francisco O'Valle
OBJECTIVE: Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of adipose-derived mesenchymal cells (ASCs) and ghrelin (GHR), a neuropeptide with neuroprotective, trophic, and developmental regulatory actions, on peripheral nerve regeneration in a model of severe nerve injury repaired with nerve conduits. MATERIAL AND METHODS: The right sciatic nerves of 24 male Wistar rats were 10-mm transected unilaterally and repaired with Dl-lactic-ε-caprolactone conduits...
September 30, 2016: Histology and Histopathology
Ilona Shapira, Nina Fainstein, Maria Tsirlin, Ilana Stav, Evgenia Volinsky, Claudia Moresi, Tamir Ben-Hur, Raphael Gorodetsky
: : Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) with no effective treatment available for the chronic-progressive stage. Cell therapy is a promising therapeutic approach for attenuating the immune-mediated CNS process. Isolated and expanded human placental stromal cells (hPSCs) possess potent immunomodulatory and trophic properties, making them a good candidate for MS therapy. We examined the potential of hPSC therapy in preventing the onset or attenuating the course of established disease in a murine MS model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis...
September 29, 2016: Stem Cells Translational Medicine
Amit Mogha, Mitchell D'Rozario, Kelly R Monk
The G protein-coupled receptor (GPCR) superfamily represents the largest class of functionally selective drug targets for disease modulation and therapy. GPCRs have been studied in great detail in central nervous system (CNS) neurons, but these important molecules have been relatively understudied in glia. In recent years, however, exciting new roles for GPCRs in glial cell biology have emerged. We focus here on the key roles of GPCRs in a specialized subset of glia, myelinating glia. We highlight recent work firmly establishing GPCRs as regulators of myelinating glial cell development and myelin repair...
September 23, 2016: Trends in Pharmacological Sciences
Osamu Imamura, Masaaki Arai, Minori Dateki, Kunio Takishima
Oligodendrocytes are the myelin-forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation. Here, we aimed to analyze the effects of donepezil on primary mouse embryonic neural stem cells (NSCs)...
September 24, 2016: Journal of Neurochemistry
Yiting Zhou, Jing Zhang, Lu Wang, Ying Chen, Yushan Wan, Yang He, Lei Jiang, Jing Ma, Rujia Liao, Xiangnan Zhang, Liyun Shi, Zhenghong Qin, Yudong Zhou, Zhong Chen, Weiwei Hu
Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion exhibits progressive white matter and cognitive impairments. However, its pathogenetic mechanisms are poorly understood. We investigated the role of interleukin-1β (IL-1β) and its receptor IL-1 receptor type 1 (IL-1R1) in an experimental SIVD model generated via right unilateral common carotid arteries occlusion (rUCCAO) in mice. We found that IL-1β expression was elevated in the corpus callosum at the early stages after rUCCAO...
September 20, 2016: Brain, Behavior, and Immunity
Pengfei Cheng, Xuzheng Zuo, Yifei Ren, Shunjie Bai, Weiju Tang, Xiuying Chen, Gong Wang, Haoxiang Wang, Wen Huang, Peng Xie
We sought to investigate the role of the adenosine A1 receptors (A1ARs) in white matter lesions under chronic cerebral hypoperfusion (CCH) and explore the potential repair mechanisms by activation of the receptors. A right unilateral common carotid artery occlusion (rUCCAO) method was used to construct a CCH model. 2-chloro-N6-cyclopentyladenosine (CCPA), a specific agonist of A1ARs, was used to explore the biological mechanisms of repair in white matter lesions under CCH. The expression of mammalian target of rapamycin (mTOR), phosphorylation of mTOR (P-mTOR), myelin basic protein (MBP, a marker of white matter myelination) were detected by Western-blot...
September 23, 2016: Neurochemical Research
Antoine Marteyn, Anne Baron-Van Evercooren
Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating leukodystrophy resulting from proteolipid protein 1 gene (PLP1) mutations leading to oligodendrocyte loss. While neuroinflammation has recently become a common feature and actor in neurodegenerative diseases, the involvement of inflammation in PMD physiopathology is still highly debated despite evidence for strong astrogliosis and microglial cell activation. Activation of the innate immune system, and more particularly, of microglia and astrocytes, is mostly associated with the deleterious role of neuroinflammation...
December 2016: Journal of Neuroscience Research
Zhan-Kui Zhao, Hong-Lian Yu, Bo Liu, Hui Wang, Qiong Luo, Xie-Gang Ding
Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties. We hypothesized that these polysaccharides resist oxidative stress-induced neuronal damage following cavernous nerve injury. In this study, rat models were intragastrically administered Lycium barbarum polysaccharides for 2 weeks at 1, 7, and 14 days after cavernous nerve injury. Serum superoxide dismutase and glutathione peroxidase activities significantly increased at 1 and 2 weeks post-injury. Serum malondialdehyde levels decreased at 2 and 4 weeks...
August 2016: Neural Regeneration Research
Guo-Min Liu, Kun Xu, Juan Li, Yun-Gang Luo
The repair of peripheral nerve injury after complete amputation is difficult, and even with anastomosis, the rapid recovery of nerve function remains challenging. Curcumin, extracted from plants of the genus Curcuma, has been shown to have anti-oxidant and anti-inflammatory properties and to improve sciatic nerve crush injury in rats. Here, we determined whether curcumin had neuroprotective effects following complete peripheral nerve amputation injury. BALB/c mice underwent complete sciatic nerve amputation, followed by an immediate epineurium anastomosis...
August 2016: Neural Regeneration Research
Li Gan, Lei Zhao, Yanteng Zhao, Ke Li, Zan Tong, Li Yi, Xiong Wang, Yinping Li, Weiqun Tian, Xiaohua He, Min Zhao, Yan Li, Yun Chen
OBJECTIVE: The objective of this work was to develop nerve guidance conduits from natural polymers, cellulose and soy protein isolate (SPI), by evaluating the effects of cellulose/SPI film-based conduit (CSFC) and cellulose/SPI sponge-based conduit (CSSC) on regeneration of nerve defects in rats. APPROACH: CSFC and CSSC with the same chemical components were fabricated from cellulose and SPI. Effects of CSSC and CSFC on regeneration of the defective nerve were comparatively investigated in rats with a 10 mm long gap in sciatic nerve...
September 21, 2016: Journal of Neural Engineering
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