Lima Rui, Gomes Eduardo D, Cibrão Jorge R, Rocha Luís A, Assunção-Silva Rita C, Rodrigues Cláudia S, Neves-Carvalho Andreia, Monteiro Susana, Salgado António J, Silva Nuno A
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
NPJ Regen Med. 2021 Mar 2;6(1):11. doi: 10.1038/s41536-021-00121-7.
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.
脊髓损伤（SCI）会导致受影响个体的运动、感觉和自主神经功能严重受损。在原发性损伤后，谷氨酸释放增加，导致兴奋性毒性和进一步的神经元死亡。因此，调节谷氨酸兴奋性毒性似乎是在损伤急性期促进神经保护的一个有前景的靶点。在本研究中，我们评估了一种美国食品药品监督管理局（FDA）批准的抗癫痫药物（左乙拉西坦-LEV）的治疗效果，该药物以与脑和脊髓中的突触囊泡蛋白SV2A结合而闻名。在两种脊髓损伤模型中测试了LEV治疗——一种影响颈椎水平，另一种影响胸椎水平的脊髓。该治疗对两种脊髓损伤模型均有效。接受治疗的动物在粗略和精细运动功能方面有显著改善。组织学评估显示空洞大小显著减小，并且接受治疗的动物中神经元和少突胶质细胞的存活率更高。分子分析表明，LEV通过稳定星形胶质细胞起作用，从而使其能够有效地从细胞外空间摄取过量的谷氨酸。总体而言，我们的结果表明左乙拉西坦可能是一种用于脊髓损伤急性期治疗的有前景的药物。
