NgR1与内源性拮抗剂LOTUS/LGI1/ADAM22调控轴突可塑性在运动训练促进脑梗死后执行功能恢复中的作用机制

执行功能障碍是影响脑卒中康复的关键因素，促进执行功能恢复的方法及机制尚未明确。我们已证实运动训练促进梗死灶周围轴突重塑及皮质红核束再生，与下调Nogo-A/NgR1/RhoA的表达有关。最近发现NgR1/ROCK与内源性拮抗剂LOTUS/LGI1/ADAM22均参与认知过程，而执行功能是高级的认知功能。据此假设，运动训练通过调控执行功能相关脑区NgR1与拮抗剂之间的平衡改善执行功能。本研究采用RHRSP tMCAO模型，观察运动训练对执行功能的影响，采用免疫荧光、BDA示踪检测皮质-丘脑-纹状体和海马轴突重塑的变化,采用免疫荧光、western blot、PCR观察Nogo-A/ROCK通路及NgR1内源性拮抗剂的表达，探讨外源性NgR1拮抗剂、ROCK抑制剂能否影响运动训练的作用，阐明运动训练对脑梗死后执行功能的影响及神经网络可塑性机制，为脑卒中后执行功能障碍的康复提供新的靶点。

Executive dysfunction is a key factor that influence rehabilitation of stroke.How to promote the recovery of executive dysfunction post stroke and what is the potential mechanism is still unknown.We have found exercise can increase the axonal plasticity and corticorubral regeneration,which was associated with the down regulation of the expression of Nogo-A/NgR1/RhoA. Recent studies indicate that both NgR1/ROCK and its endogenous antagonist LOTUS/LGI1/ADAM22 are involved in cognition.Executive functions are higher order cognitive processes.Our hypothesis is that exercise can improve executive functions after cerebral ischemia through modulation of the balance between NgR1 pathway and LOTUS/LGI1/ADAM22.In this study, transient MCAO RHRSP model will be used. The effect of exercise on executive functions will be evaluated.Immunofluorescence,BDA fiber tracing will be used to detect the axonal remodeling in cortical-thalamus-striatum and hippocampus.The expression of Nogo-A/NgR1/RhoA/ROCK and NgR1 engogenous antagonists will be demonstrated by immunofluorescence, western blot，PCR.Exogenous antagonist of NgR1, ROCK inhibitor will be delivered to explore if the effecte of exercise can be changed.In this way, the effect of exercise on executive functions and the mechanism of neural network plasticity will be demonstrated.The study will provide a new target of executive function rehabilitation post stroke.