Brief electrical nerve stimulation enhances intrinsic repair capacity of the focally demyelinated central nervous system  

作　　者：Lydia Ayanwuyi Nataliya Tokarska Nikki A.McLean Jayne M.Johnston Valerie M.K.Verge 

机构地区：[1]Department of Anatomy,Physiology and Pharmacology,University of Saskatchewan,Saskatoon,SK,Canada [2]Cameco MS Neuroscience Research Center,University of Saskatchewan,Saskatoon,SK,Canada

出　　处：《Neural Regeneration Research》2022年第5期1042-1050,共9页中国神经再生研究（英文版）

基　　金：supported by Multiple Sclerosis Society of Canada(MSSOC),No.2362(to VMKV);Canadian Institutes of Health Research(CIHR),No.14238(to VMKV);were supported by University of Saskatchewan College of Medicine Research Awards(Co MGRADs)。

摘　　要：Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-protective phenotype and shifting macrophages from a predominantly pro-inflammatory toward a pro-repair phenotype.Whether this same potential exists in the central nervous system is not known.Thus,for proof of principle studies,the peripheral nerve demyelination and ES model was adapted to the central nervous system,whereby a unilateral focal LPC-induced demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter was created,so that subsequent ipsilateral sciatic nerve ES results in increased neural activity in the demyelinated axons.Data reveal a robust focal demyelination at 7 days post-LPC injection.Delivery of 1-hour ES at 7 days post-LPC polarizes macrophages/microglia toward a pro-repair phenotype when examined at 14 days post-LPC;results in smaller LPC-associated regions of inflammation compared to non-stimulated controls;results in significantly more cells of the oligodendroglial lineage in the demyelinated region;elevates myelin basic protein levels;and shifts the paranodal protein Caspr along demyelinated axons to a more restricted distribution,consistent with reformation of the paranodes of the nodes of Ranvier.ES also significantly enhanced levels of phosphorylated neurofilaments detected in the zones of demyelination,which has been shown to confer axon protection.Collectively these findings support that strategies that increase neural activity,such as brief electrical stimulation,can be beneficial for promoting intrinsic repair following focal demyelinating insults in demyelinating diseases such as multiple sclerosis.All animal procedures performed were approved by the University of Saskatchewan's Animal Research Ethics Board(protocol#20090087;last approval date:November 5,2020).

关 键 词：axon protection DEMYELINATION immune response lysophosphatidyl choline macrophage microglia multiple sclerosis MYELIN nervous system repair neural activity polarization 

分 类 号：R744.5[医药卫生—神经病学与精神病学]