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Nimodipine reduces dysfunction and demyelination in models of multiple sclerosis

Desai, RA; Davies, AL; Del Rossi, N; Tachrount, M; Dyson, A; Gustavson, B; Kaynezhad, P; ... Smith, KJ; + view all (2020) Nimodipine reduces dysfunction and demyelination in models of multiple sclerosis. Annals of Neurology , 88 (1) pp. 123-136. 10.1002/ana.25749. Green open access

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Abstract

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. This article is protected by copyright. All rights reserved.

Type: Article
Title: Nimodipine reduces dysfunction and demyelination in models of multiple sclerosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/ana.25749
Publisher version: https://doi.org/10.1002/ana.25749
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10095107
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