运动康复训练结合小胶质细胞及巨噬细胞调控对脊髓损伤后运动神经环路的作用及其机制研究

脊髓损伤的康复研究发现运动康复训练及抗炎药物治疗有利于神经修复，并能提高日常生活能力，减少并发症。我们前期的研究分别发现脊髓损伤大鼠经运动康复训练及靶向调控小胶质细胞及巨噬细胞均能提高其运动功能。本课题将首次利用化学遗传学技术特异靶向抑制脊髓损伤大鼠损伤部位的小胶质细胞及巨噬细胞的活化，同时结合运动康复训练处理脊髓损伤。通过免疫荧光及免疫印迹技术观察损伤局部脊髓兴奋性/抑制性中间神经元比（E/I）的变化；应用神经顺行、逆行示踪技术观察皮质脊髓束神经运动环路结构改变。期待阐明经调控小胶质细胞及巨噬细胞改善损伤部位免疫微环境，结合康复训练诱导正确神经再生及其连接途径。以探索运动康复训练及药物抗炎治疗组合疗法的神经重塑作用，并探讨该组合治疗的作用机制，为脊髓损伤运动康复治疗提供新途径。

Anti-inflammatory with drug and rehabilitation training after spinal cord injury (SCI) can promote neurological recovery, reduce complications and improve patients' daily living ability. Our previous studies have shown that exercise rehabilitation training and targeted regulation of microglia and macrophages in rats can improve motor function after SCI. This project will use chemical genetic technology to specifically target the activation and infiltration of microglial and macrophage combined with rehabilitation training to detect the neural activity of SCI rats. The changes in excitability/inhibition ratio (E/I) of intermediate neurons in the spinal cord are detected by immunofluorescence and WB technology; nerve antegrade and retrograde tracing techniques are used to observe the changes in the structure of the neuromotor circuit of the entire corticospinal tract and explore the neural remodeling after this combination treatment. Finally, it is supposed that the regulation of microglia and macrophages would improve the immune microenvironment at the injury site, combined with rehabilitation training would further guides the correct neural connection pathways, hence contribute to neural regeneration. This project will propose new perspectives on the mechanism of such combination treatment in pre-clinical research, and provides new approaches to improve motor function after spinal cord injury.