血脑屏障损伤在慢性脑低灌注所致的神经网络与认知损害中的作用研究

血脑屏障（BBB）损伤是脑损伤性疾病常有的早期改变。已有研究显示，慢性脑低灌注是 AD和VaD共同的病理生理基础和早期生物标志，并损害BBB。但BBB损伤在神经网络与认知损害中的作用尚未阐明。本项目组前期研究显示，慢性脑低灌注可导致海马及相关脑区的结构神经网络与认知损害。因此推测，在慢性脑低灌注状态下，BBB损伤可能是早期介导结构与功能神经网络损害的关键因素，最终导致认知损害。本研究拟建立大鼠慢性脑低灌注模型，动态观察脑血流量降低后不同时相BBB和认知功能变化；采用DTI评估结构神经网络完整性；采用BOLD-fMRI评估包括DMN在内的功能神经网络。通过对上述指标不同时间序列的纵向对比并观察BBB保护剂干预前后变化，从分子、网络和整体水平动态研究BBB在慢性脑低灌注所致的神经网络与认知损害中的作用及其机制，寻找可干预的关键性靶点，为慢性脑低灌注相关的AD和VaD早期防治提供新的理论依据。

Blood brain barrier is an early and common change of many brain diseases.Chronic cerebral hypoperfusion is the common pathophysiological basis and early biomarker of Alzheimer’s Disease and vascular dementia, and at the same time, it can destroy the blood brain barrier(BBB). However, the role and the mechanism of BBB dysfunction in the process of brain network destruction and cognitive impairment remains elusive. Our preliminary studies show that chronic cerebral hypoperfusion can cause brain structural network destruction and cognitive impairment in hippocampus and related brain regions. We hypothesize that BBB dysfunction，in an early phase, can mediate the brain structural and functional network destruction and finally lead to cognitive impairment. In this study, BBB complicity and cognitive function in different phases will be evaluated in the chronic cerebral hypoperfused rats model; DTI sequence will be used for the brain structural network evaluation and BOLD-fMRI will be used for the functional network, including the DMN. By comparing the above indicators in different time series and observing the changes after using the BBB protectant, the present research will try to elucidate the impact of BBB dysfunction on the brain network destruction and cognitive impairment in the chronic cerebral hypoperfused model in the molecular, the network and the whole view. At the same time, we hope to find a key target for the intervention through the pass way. All this will be helpful for the intervention of chronic cerebral hypoperfusion related AD and VaD.