Nimodipine reduces dysfunction and demyelination in models of multiple sclerosis

Desai, R. A. et al. (2020) Nimodipine reduces dysfunction and demyelination in models of multiple sclerosis. Annals of Neurology, 88(1), pp. 123-136. (doi: 10.1002/ana.25749) (PMID:32293054)

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Objective: Treatment of relapses in multiple sclerosis (MS) has not advanced beyond steroid use, which reduces acute loss of function, but has little effect on residual disability. Acute loss of function in an MS model (experimental autoimmune encephalomyelitis; EAE) is partly due to CNS hypoxia, and function can promptly improve upon breathing oxygen. Here we investigate the cause of the hypoxia and whether it is due to a deficit in oxygen supply arising from impaired vascular perfusion. We also explore whether the CNS‐selective vasodilating agent, nimodipine, may provide a therapy to restore function, and protect from demyelination in two MS models. Methods: A variety of methods have been employed to measure basic cardiovascular physiology, spinal oxygenation, mitochondrial function and tissue perfusion in EAE. Results: We report that the tissue hypoxia in EAE is associated with a profound hypoperfusion of the inflamed spinal cord. Treatment with nimodipine restores spinal oxygenation and can rapidly improve function. Nimodipine therapy also reduces demyelination in both EAE, and a model of the early MS lesion. Interpretation: Loss of function in EAE, and demyelination in EAE and the model early MS lesion, appear to be due, at least in part, to tissue hypoxia due to local spinal hypoperfusion. Therapy to improve blood flow not only protects neurological function, but also reduces demyelination. We conclude that nimodipine could be repurposed to offer substantial clinical benefit in MS.

Item Type:Articles
Additional Information:The authors acknowledge funding support from the Multiple Sclerosis Society, UK, Fondation Leducq, National Multiple Sclerosis Society, USA, Rosetrees Trust, The Wellcome Trust (104580/Z/14/Z).
Glasgow Author(s) Enlighten ID:Harvey, Professor Andy and Van Der Putten, Miss Marieke
Authors: Desai, R. A., Davies, A. L., Del Rossi, N., Tachrount, M., Dyson, A., Gustavson, B., Kaynezhad, P., Mackenzie, L., van der Putten, M. A., McElroy, D., Schiza, D., Linington, C., Singer, M., Harvey, A. R., Tachtsidis, I., Golay, X., and Smith, K. J.
College/School:College of Science and Engineering > School of Physics and Astronomy
Journal Name:Annals of Neurology
ISSN (Online):1531-8249
Published Online:15 April 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Annals of Neurology 88(1): 123-136
Publisher Policy:Reproduced under a Creative Commons License

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