Deng Wei-Wei, Wu Guang-Yan, Min Ling-Xia, Feng Zhou, Chen Hui, Tan Ming-Liang, Sui Jian-Feng, Liu Hong-Liang, Hou Jing-Ming
Department of Rehabilitation, Southwest Hospital, Army Medical University, Chongqing, China.
Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Front Neurosci. 2021 Apr 9;15:640255. doi: 10.3389/fnins.2021.640255. eCollection 2021.
Although spinal cord injury (SCI) is the main cause of disability worldwide, there is still no definite and effective treatment method for this condition. Our previous clinical trials confirmed that the increased excitability of the motor cortex was related to the functional prognosis of patients with SCI. However, it remains unclear which cell types in the motor cortex lead to the later functional recovery. Herein, we applied optogenetic technology to selectively activate glutamate neurons in the primary motor cortex and explore whether activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI in rats and the preliminary neural mechanisms involved. Our results showed that the activation of glutamate neurons in the motor cortex could significantly improve the motor function scores in rats, effectively shorten the incubation period of motor evoked potentials and increase motor potentials' amplitude. In addition, hematoxylin-eosin staining and nerve fiber staining at the injured site showed that accurate activation of the primary motor cortex could effectively promote tissue recovery and neurofilament growth (GAP-43, NF) at the injured site of the spinal cord, while the content of some growth-related proteins (BDNF, NGF) at the injured site increased. These results suggested that selective activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI and may be of great significance for understanding the neural cell mechanism underlying functional recovery induced by motor cortex stimulation.
尽管脊髓损伤（SCI）是全球致残的主要原因，但对于这种病症仍没有明确有效的治疗方法。我们之前的临床试验证实，运动皮层兴奋性增加与SCI患者的功能预后相关。然而，运动皮层中哪些细胞类型导致后期功能恢复仍不清楚。在此，我们应用光遗传学技术选择性激活初级运动皮层中的谷氨酸能神经元，探讨初级运动皮层中谷氨酸能神经元的激活是否能促进大鼠SCI后的功能恢复以及涉及的初步神经机制。我们的结果表明，运动皮层中谷氨酸能神经元的激活可显著提高大鼠的运动功能评分，有效缩短运动诱发电位的潜伏期并增加运动电位的幅度。此外，损伤部位的苏木精-伊红染色和神经纤维染色显示，精确激活初级运动皮层可有效促进脊髓损伤部位的组织恢复和神经丝生长（GAP-43、NF），同时损伤部位一些生长相关蛋白（BDNF、NGF）的含量增加。这些结果表明，选择性激活初级运动皮层中的谷氨酸能神经元可促进SCI后的功能恢复，可能对理解运动皮层刺激诱导功能恢复的神经细胞机制具有重要意义。
