慢性脑低灌注导致的血管性认知功能损害(vascular cgnitive impairment, VCI)是老年期痴呆常见临床类型阿尔茨海默病与血管性痴呆共有的重要病理基础。内源性神经发生作为神经环路可塑性的重要形式与认知功能密切相关，这一重要发现为认知保护研究带来新的契机。我们前期研究发现慢性脑低灌注大鼠海马齿状回颗粒下区新生神经元数目显著增加，经当归干预后该现象更为明显。那么，神经发生是否是慢性脑低灌注的关键代偿性的内源性认知保护机制？而当归的认知改善功效是否主要通过影响神经发生而起作用？都是非常值得研究的焦点问题。因此本项目拟采用慢性脑低灌注大鼠模型模拟 VCI，从整体认知、电生理、细胞和分子等不同水平和角度探讨内源性神经发生在VCI中的认知保护效应及其在当归治疗VCI 中的作用和机制，以期从潜在的关键靶点与药物干预两方面为 VCI及其相关的老年期痴呆的研究和防治提供新的理论依据。

The pathophysiological change underlying vascular cognitive impairment (VCI), induced by chronic cerebral hypoperfusion, is an important common feature in Alzheimer's disease and vascular dementia. Endogenous neurogenesis, the foundation of neural circuit plasticity, has been reported to closely relate to cognition. This phenomenon paves new insights to the study of cognitive protection. In our previous studies, the number of neogenetic neurons increased significantly in the subgranular zone in the dentate gyrus of the hippocampus of chronic cerebral hypoperfused rats, and the increment was augmented after Angelica treatment. Therefore, is endogenous neurogenesis the fundamental compensation for the cognitive impairment in VCI? Does the protective effect of Angelica on cognition take through increasing neurogenesis? To answer these two questions, chronic cerebral hypoperfused rats will be used as the model of VCI and get Angelica treatment. Investigation will be done through different levels, including behavioral change, electrophysiological recording from brain slices, quality and quantity of neogenetic neurons and the expression of the key cognition related molecules. The prospect of the present project is to verify endogenous neurogenesis as a key compensative factor of cognition in VCI and associated dementia in the elderly, and as the potential target in Angelica therapy.