2-Cl-MGV-1介导BDNF-TrkB通路调控脑梗死后远隔脑区神经再生并改善认知损害的研究

脑皮层梗死后，认知相关远隔脑区（如丘脑和海马）继发性损害参与了卒中后认知障碍的发生发展，但对此缺乏根本有效的防治措施。我们前期研究并发表论文证实，2-Cl-MGV-1可减少脑梗死后远隔脑区神经元凋亡并改善认知，但是否同时促进局部神经再生及其机制尚不清楚。新近，我们观察到2-Cl-MGV-1可增加脑梗死后远隔脑区BDNF及其受体TrkB表达和促进神经元再生，提示其可能介导BDNF-TrkB通路，促神经再生而最终改善认知。因此，本项目拟建立高血压大鼠大脑皮层梗死模型，观察2-Cl-MGV-1干预前后认知功能、认知相关远隔脑区神经元再生及BDNF-TrkB通路相关蛋白的改变；再以252a阻断BDNF-TrkB通路，评估脑梗死后上述脑区神经再生和认知改善是否受阻，以明确远隔脑区神经再生受限是否参与脑梗死后认知障碍，并揭示2-Cl-MGV-1的作用机制，以期为脑梗死后认知障碍的防治提供新思路。

Secondary damage of cognitive-related remote brain regions such as the thalamus and the hippocampus is involved in the occurrence and development of post-stroke cognitive deficits after cortical infarction. However, it still lacks fundamentally effective prevention and treatment measures for this secondary damage. Our previous study and published article have found that 2-Cl-MGV-1 reduced neuronal apoptosis in remote brain regions and ameliorated cognitive deficits after cerebral infarction, but whether it also promotes post-stroke neurogenesis in these brain regions and its mechanisms remain unknown. Recently, we have observed in the preliminary experiments that 2-Cl-MGV-1 increased the expression of BDNF and its receptor TrkB, and stimulated neurogenesis in the remote brain regions after cerebral infarction. This suggested that 2-Cl-MGV-1 might promote neurogenesis through the BDNF-TrkB signal pathway and ameliorate post-stroke cognitive deficits. Therefore, the present project is designed to firstly establish cortical infarction in hypertensive rats, and then evaluate the change of post-stroke cognition, neurogenesis in the cognitive-related remote brain regions and the protein levels associated with the BDNF-TrkB signal pathway before and after administration of 2-Cl-MGV-1. We further apply 252a to block the BDNF-TrkB signal pathway, and access whether neurogenesis in the above remote brain regions and the amelioration of post-stroke cognitive deficits are inhibited. Findings from the present project would help to make clear the role of neurogenesis in remote brains regions on post-stroke cognitive deficits and further reveal the mechanisms of 2-Cl-MGV-1, which would finally provide novel ideas for the prophylaxis and treatment of post-stroke cognitive deficits.