RN及RNp-IO通路重塑调控CIMT介导的脑卒中后运动功能恢复的机制研究

脑卒中发病率高、致残率高，强制性运动训练（constraint-induced movement therapy，CIMT）可有效促进脑卒中后运动功能的恢复，但起效机制尚不明确。我们前期研究发现，CIMT能够促进大脑皮层激活与红核（red nucleus，RN）重塑，而RN主要接受来自大脑皮层和小脑兴奋性纤维的调控，RNp（RN小细胞部）至下橄榄核（IO）的投射为RN主要传出通路之一，调控运动学习行为。因而，我们提出“CIMT通过促进双侧RN激活，促进双侧RNp-IO通路的激活和重塑，从而促进脑卒中后运动功能恢复”的假说。本研究拟采用光遗传学技术抑制/激活RN、神经示踪与药理遗传学技术观察并特异性阻断RNp-IO投射通路，探索RN激活对运动功能恢复及CIMT疗效的影响，验证RNp-IO通路与CIMT疗效间的因果关系。对阐明CIMT介导的运动功能恢复背后的锥体外系重塑机制有重要意义。

Stroke is characterized by high incidence and rate of disability..Constraint-induced movement therapy (CIMT) can effectively promote the recovery of motor function after stroke, but the mechanism remains unclear. In our previous studies, CIMT promoted the activation of cerebral cortex and the remodeling of red nucleus (RN). RN is mainly regulated by excitatory fibers from cerebral cortex and cerebellum. Projection of RNp (parvocellular part of RN) to inferior olivary nucleus (IO) is one of the main efferent pathways of RN, which regulates motor learning behavior. Therefore, we proposed the hypothesis that "CIMT promotes the activation and remodeling of bilateral RNp-IO pathway through promoting bilateral RN activation, thus promoting the recovery of motor function after stroke". In this study, optogenetic techniques were used to inhibit/activate RN, anterograde neural tracing and pharmacological genetics techniques were used to observe and specifically block RNp-IO pathway, so as to explore the influence of RN activation on motor function recovery and the efficacy of CIMT, and clarify the causal link between the RNp-IO pathway and CIMT-induced motor functional recovery after cerebral ischemia. It’s of great importance to the elucidate of the mechanism of extrapyramidal remodeling behind the CIMT-induced motor function recovery.