随着人口老龄化进程加快, 痴呆已成为影响我国国民健康的严重公共卫生问题。反复低血糖是导致痴呆发生发展的重要危险因素，但目前没有可消除由低血糖引发的难逆性脑损害的调控手段，由低血糖引发的神经血管单元损伤的潜在分子机制也不明确。我们在以往研究基础上，以低糖应激为危险因素，将脑血管内皮细胞TIGAR信号作为切入点开展深入探索：(1) 阐明低糖应激损伤后脑血管内皮细胞TIGAR信号依存的磷酸戊糖途径与紧密连接蛋白损伤的关联性；(2) 多角度考察低糖应激损伤下脑血管内皮TIGAR信号调控失衡与中隔野/海马投射环路神经元的细胞间病理通讯机制；(3) 针对脑微血管内皮细胞TIGAR的上、下游信号分子事件，考察药理学调控是否起到改善认知功能障碍作用。本课题通过揭示低糖应激损伤条件下神经血管单元损伤模式及规律，为寻找防治痴呆的药物新靶点提供实验依据和研究新思路。

The prevalence of dementia in aging population has become a much concerned public health problem in China. Hypoglycemia is one of the most important risk factors to induce a series of neurological symptoms, which may finally lead to cognitive dysfunction. However, its precise molecular mechanism remains largely unknown. Based on our previous studies, we are going to take hypoglycemia induced stress as a risk factor, to elucidate the role of endothelial TIGAR signals in metabolic stress-induced neurovascular unit injury. Firstly, we explore the relevance between the TIGAR-dependent pentose phosphate pathway and tight junction injury in brain endothelial cells. Secondly, we address the mechanism which elicits intercellular communication between endothelial TIGAR and septo-hippocampal cholinergic neurons. Finally, the present study will investigate whether improvement of endothelial TIGAR can rescue cognitive impairments. Unraveling the role of TIGAR-dependent signaling during hypoglycemia-mediated metabolic stress may lead to the development of novel protective strategies via restorative therapies for cognitive dysfunction.