糖尿病合并脑血管病的发生随增龄而升高，但糖尿病加重缺血性中风的神经损伤机制仍不清楚。NRSF/REST是维持正常脑功能所必需的转录蛋白，其异常表达和分布与多种神经系统疾病有关，我们前期研究发现，其表达水平在糖尿病小鼠脑内显著升高，且可能影响了神经保护药物G-CSF对糖尿病中风的保护作用，推测糖尿病可能通过NRSF/REST而加重缺血性神经损伤。本项目拟在整体与离体的糖尿病及糖尿病合并缺血性中风损伤模型上，探讨糖代谢紊乱对NRSF/REST表达、定位及功能的影响，观察 NRSF/REST在糖尿病及糖尿病中风中对BDNF、NMDA受体及AMPA受体的调控、以及对神经元/血管内皮细胞信息交流的影响。本项目首次提出糖代谢紊乱可通过影响NRSF/REST、破坏神经元/血管内皮细胞信息交流而加重脑缺血损伤，研究结果将进一步阐释糖尿病加重脑缺血损伤的机理，也为糖尿病中风的临床治疗提供新的思路。

Diabetes not only increases the risk but also worsens the neuronal injury after ischemic stroke. However, the underlying mechanisms remain unclear. Our previous work demonstrated that neuron-restrictive silence factor (NRSF/REST) levels significantly increase in diabetic mice brain, suggesting a possible role of NRSF/REST in silencing series neuronal genes expression and ultimately worsens the recovery. Here, with in vivo and in vitro diabetic model, and diabetic ischemic stroke model as well, we try to investigate how the dysfunction of glucose metabolism modulate the expression, location and function of NRSF/REST. Meanwhile, we will observe the effect of NRSF/REST under diabetes or diabetic ischemic stroke on BDNF, NMDAR and AMPAR, and on the interaction of neurons and vascular endothelium. Our results will further clarify why diabetes worsen ischemic neuronal injury. Moreover, these results might put forward new clues for clinic therapy.