脑梗死后认知障碍与远离缺血灶的丘脑继发损害有关，其机制不明，Aβ沉积被认为是关键因素。我们前期研究证实，Aβ沉积也是大脑皮层梗死后丘脑继发损害的重要病理特征，减轻丘脑继发损害可改善认知功能，提示丘脑Aβ沉积与脑梗死后认知障碍有关。然而导致脑梗死后丘脑Aβ沉积的机制未明。目前发现血脑屏障LRP1和glymphatic系统受损是脑内Aβ沉积的主要机制，预实验也观察到脑梗死后丘脑血脑屏障LRP1和glymphatic系统受损，其是否也介导了丘脑Aβ沉积并导致脑梗死后认知障碍尚不明确。本项目拟采用高血压大鼠建立大脑皮层梗死模型，证实丘脑血脑屏障LRP1及glymphatic系统受损；进而通过调控LRP1和AQP4基因表达为切入点，探讨大脑皮层梗死后血脑屏障LRP1和glymphatic系统受损在丘脑Aβ沉积中的作用及其与脑梗死后认知障碍的关系，以揭示其发生机制，为脑梗死后认知障的防治提供新策略。

Post-stroke cognitive impairment was associated with the secondary damage in the thalamus. The underlying mechanisms remain unclear and Aβ deposition was considered to be the key factor involved in the post-stroke cognitive impairment. Our previous studies confirmed that Aβ deposition was the significant pathologic feature in the secondary thalamic damage after cerebral cortex infarction, and interventions ameliorating this damage could improve cognitive function, which indicated that Aβ deposition in the thalamus might be related with post-stroke cognitive impairment. However, it is unclear how Aβ accumulation is triggered and regulated in the thalamus following cerebral infarction. Currently, the dysfunction of blood-brain barrier LRP1 and glymphatic system are identified as the primary mechanism of Aβ deposition in the brain. Our preliminary experiment also observed that the blood-brain barrier LRP1 and glymphatic system were impaired in the thalamus after cortical infarction. It remains unclear whether the dysfunction of blood-brain barrier LRP1 and glymphatic system mediated Aβ deposition in the thalamus and led to post-stroke cognitive impairment. To address these issues, the present project is firstly designed to confirm that the dysfunction of blood-brain barrier LRP1 and glymphatic system are existed in the thalamus using the cortical infarction model in hypertensive rats. Further, by means of regulating the gene expression of LRP1 and AQP4, we wish to investigate the roles of the dysfunction of blood-brain barrier LRP1 and glymphatic system in Aβ deposition in the thalamus secondary to cerebral cortex infarction and their relationship with post-stroke cognitive impairment. Findings from the present proposal would help to elucidate the potential mechanism underlying post-stroke cognitive impairment and provide new strategies for the prophylaxis and treatment of post-stroke cognitive impairment.