Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord

Abstract Spinal cord injury (SCI) leads to dramatic impairments of motor, sensory, and autonomic functions of affected individuals. Following the primary injury, there is an increased release of glutamate that leads to excitotoxicity and further neuronal death. Therefore, modulating glutamate excito...

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Autores principales:	Rui Lima, Eduardo D. Gomes, Jorge R. Cibrão, Luís A. Rocha, Rita C. Assunção-Silva, Cláudia S. Rodrigues, Andreia Neves-Carvalho, Susana Monteiro, António J. Salgado, Nuno A. Silva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/6381c90cd2744b65acae2876e1faad97
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spelling	oai:doaj.org-article:6381c90cd2744b65acae2876e1faad972021-12-02T14:40:11ZLevetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord10.1038/s41536-021-00121-72057-3995https://doaj.org/article/6381c90cd2744b65acae2876e1faad972021-03-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00121-7https://doaj.org/toc/2057-3995Abstract Spinal cord injury (SCI) leads to dramatic impairments of motor, sensory, and autonomic functions of affected individuals. Following the primary injury, there is an increased release of glutamate that leads to excitotoxicity and further neuronal death. Therefore, modulating glutamate excitotoxicity seems to be a promising target to promote neuroprotection during the acute phase of the injury. In this study, we evaluated the therapeutic effect of a FDA approved antiepileptic drug (levetiracetam-LEV), known for binding to the synaptic vesicle protein SV2A in the brain and spinal cord. LEV therapy was tested in two models of SCI—one affecting the cervical and other the thoracic level of the spinal cord. The treatment was effective on both SCI models. Treated animals presented significant improvements on gross and fine motor functions. The histological assessment revealed a significant decrease of cavity size, as well as higher neuronal and oligodendrocyte survival on treated animals. Molecular analysis revealed that LEV acts by stabilizing the astrocytes allowing an effective uptake of the excess glutamate from the extracellular space. Overall, our results demonstrate that Levetiracetam may be a promising drug for acute management of SCI.Rui LimaEduardo D. GomesJorge R. CibrãoLuís A. RochaRita C. Assunção-SilvaCláudia S. RodriguesAndreia Neves-CarvalhoSusana MonteiroAntónio J. SalgadoNuno A. SilvaNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Rui Lima Eduardo D. Gomes Jorge R. Cibrão Luís A. Rocha Rita C. Assunção-Silva Cláudia S. Rodrigues Andreia Neves-Carvalho Susana Monteiro António J. Salgado Nuno A. Silva Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord
description	Abstract Spinal cord injury (SCI) leads to dramatic impairments of motor, sensory, and autonomic functions of affected individuals. Following the primary injury, there is an increased release of glutamate that leads to excitotoxicity and further neuronal death. Therefore, modulating glutamate excitotoxicity seems to be a promising target to promote neuroprotection during the acute phase of the injury. In this study, we evaluated the therapeutic effect of a FDA approved antiepileptic drug (levetiracetam-LEV), known for binding to the synaptic vesicle protein SV2A in the brain and spinal cord. LEV therapy was tested in two models of SCI—one affecting the cervical and other the thoracic level of the spinal cord. The treatment was effective on both SCI models. Treated animals presented significant improvements on gross and fine motor functions. The histological assessment revealed a significant decrease of cavity size, as well as higher neuronal and oligodendrocyte survival on treated animals. Molecular analysis revealed that LEV acts by stabilizing the astrocytes allowing an effective uptake of the excess glutamate from the extracellular space. Overall, our results demonstrate that Levetiracetam may be a promising drug for acute management of SCI.
format	article
author	Rui Lima Eduardo D. Gomes Jorge R. Cibrão Luís A. Rocha Rita C. Assunção-Silva Cláudia S. Rodrigues Andreia Neves-Carvalho Susana Monteiro António J. Salgado Nuno A. Silva
author_facet	Rui Lima Eduardo D. Gomes Jorge R. Cibrão Luís A. Rocha Rita C. Assunção-Silva Cláudia S. Rodrigues Andreia Neves-Carvalho Susana Monteiro António J. Salgado Nuno A. Silva
author_sort	Rui Lima
title	Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord
title_short	Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord
title_full	Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord
title_fullStr	Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord
title_full_unstemmed	Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord
title_sort	levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6381c90cd2744b65acae2876e1faad97
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Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord

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