RT Journal Article
SR Electronic
T1 Early delivery and prolonged treatment with nimodipine prevents the development of spasticity after spinal cord injury in mice
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP eaay0167
DO 10.1126/scitranslmed.aay0167
VO 12
IS 539
A1 Marcantoni, Maite
A1 Fuchs, Andrea
A1 Löw, Peter
A1 Bartsch, Dusan
A1 Kiehn, Ole
A1 Bellardita, Carmelo
YR 2020
UL http://stm.sciencemag.org/content/12/539/eaay0167.abstract
AB 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.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.