Research ArticleSpinal Cord Injury

Early delivery and prolonged treatment with nimodipine prevents the development of spasticity after spinal cord injury in mice

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Science Translational Medicine  15 Apr 2020:
Vol. 12, Issue 539, eaay0167
DOI: 10.1126/scitranslmed.aay0167

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Preventing spinal cord injury comorbidity

Subjects with spinal cord injury (SCI) often develop spasticity, a condition in which an increase in muscle tone causes continuous muscle contraction. Strategies for treating spasticity are lacking. Now, Marcantoni et al. investigated the mechanisms mediating spasticity in a mouse model of chronic SCI and showed that the L-type calcium channel CaV1.3 is involved in the development of this condition. Treating animals early after SCI with nimodipine, an L-type calcium channel blocker approved for the treatment of brain hemorrhage, prevented the development of spasticity in mice. Early prolonged blockade of L-type calcium channels might be effective for preventing spasticity in subjects with SCI.

Abstract

Spasticity, one of the most frequent comorbidities of spinal cord injury (SCI), disrupts motor recovery and quality of life. Despite major progress in neurorehabilitative and pharmacological approaches, therapeutic strategies for treating spasticity are lacking. Here, we show in a mouse model of chronic SCI that treatment with nimodipine—an L-type calcium channel blocker already approved from the European Medicine Agency and from the U.S. Food and Drug Administration—starting in the acute phase of SCI completely prevents the development of spasticity measured as increased muscle tone and spontaneous spasms. The aberrant muscle activities associated with spasticity remain inhibited even after termination of the treatment. Constitutive and conditional silencing of the L-type calcium channel CaV1.3 in neuronal subtypes demonstrated that this channel mediated the preventive effect of nimodipine on spasticity after SCI. This study identifies a treatment protocol and suggests that targeting CaV1.3 could prevent spasticity after SCI.

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