慢性脑缺血可诱导脑循环障碍和神经细胞损害，是导致患者认知功能障碍的重要因素，其作用机制尚不明确，临床上缺乏有效的干预措施。我们前期研究显示：通过纳米纤维膜局部负载缓释血管内皮生长因子（VEGF）调控的血管重建，可有效促进重建血管生成，改善缺血区脑循环;同时内源性大麻素系统中脂肪酰胺水解酶（FAAH）抑制剂URB597可改善慢性脑缺血动物的认知功能障碍。本项目基于神经血管单元理念，进一步研究缓释VEGF调控的血管重建及URB597联合应用，改善慢性脑缺血性认知功能障碍的协同神经保护作用及其相关机制。本项目拟通过体内外实验，采用神经组织学、神经行为学、神经电生理学、脑血流动力学、分子生物学等多种技术手段，考察联合应用缓释外源性VEGF调控的血管重建与激活内源性神经保护的化合物URB597，对慢性脑缺血性认知功能障碍的神经保护作用及相关机制，为缺血性神经元损伤修复和功能重建提供新的干预途径。

Chronic cerebral ischemia may induce disturbance of cerebral circulation and neuronal damage associated with cognitive impairment, but its mechanism of the action is still unclear. It remains unknown how to prevent and treat the cognitive deterioration in patients with chronic cerebral ischemia clinically. Our previous studies indicated that nano-fiber memberane locally loaded by sustained release vascular endothelial growth factor（VEGF）regulation of vascular reconstruction lead to angiogenesis effectively for improving the cerebral circulation in the ischemic cerebral regions and treatment of URB597, a selective inhibitor of fatty acid amide hydrolyase (FAAH) for the degradation of endocannabinoid ligands, can improve the cognitive dysfunction in rats with chronic cerebral ischemia. Based on the conception of neuro-vascular unit, we will further study whether the application of combining sustained release VEGF regulation of vascular reconstruction with URB597 exists the synergistic neuroprotective effect on ischemic cognitive deficits and its related mechanisms. In this study, we will investigate the neuroproective effects of both exogenous sustained release VEGF regulation of vascular network reconstruction and enhanced endogenous neuroprotective compound URB597 on chronic ischemic cognitive dysfunction and its mechanism using neuronal histology, neuronal behavior，neuronal electrophysiology, cerebral hemodynamics and molecular biology in vivo and vitro experiments. This study will enable us to find a novel strategy for the repair of ischemic neuronal injury and reconstruction of neuronal function.