036 – Electrical nerve stimulation promotes repair and confers an axon-protective state following a focal demyelinating lesion

Printed Poster | Session 2

036 – Electrical nerve stimulation promotes repair and confers an axon-protective state following a focal demyelinating lesion

Nataliya Tokarska (1) – Lydia Ayanwuyi (1) – Nikki M McLean (1) – Valerie MK Verge (1)
Cameco MS Neuroscience Research Center, Anatomy, Physiology and Pharmacology/College of Medicine/University of Saskatchewan, Saskatoon, Canada (1)


MS is an inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration. Efficient repair of demyelinated lesions is one of the major challenges of MS. Our lab focusses on therapies that enhance intrinsic repair mechanisms of the peripheral and central nervous system following injury. We have 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 (M1) toward a pro-repair (M2) phenotype. We have adapted this model to the CNS, creating a unilateral focal LPC demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter, so that subsequent sciatic nerve ES results in increased neural activity in the demyelinated axons. Preliminary data reveals a robust focal demyelination at 7 days post-LPC injection. Delivery of 1hr ES at 7d post-LPC, polarizes macrophages/microglia toward a pro-repair M2 phenotype, evident as early as 2d post-ES (12d post-LPC), and still apparent in ES animals at the latest time examined, 14d post-LPC. ES also resulted in smaller regions of inflammation compared to non-stimulated controls; the recruitment of significantly more OPCs to the demyelinated region; more effective remyelination, with the paranodal protein Caspr along demyelinated axons 14d post-LPC, shifting to a more restricted distribution, consistent with reformation of the nodes of Ranvier; and enhanced levels of phosphorylated NFMs, supporting promotion of an axon protective state. Collectively this supports that strategies that increase neural activity can be beneficial for repair following focal demyelinating insults. We are grateful for support from the MS Society of Canada, and the Colleges of Medicine and Graduate and Postdoctoral Studies at the University of Saskatchewan.