咬合支持丧失可导致认知功能障碍，但机制尚不明确。本课题组前期研究证实咬合丧失会加重慢性脑缺血引起的认知障碍，一氧化氮(NO)信号通路在此过程中起重要作用，它与小胶质细胞-星形胶质细胞构成的胶质细胞网关系密切，据此提出假设：咬合支持丧失加重慢性脑缺血性认知损害可能通过胶质细胞网发挥作用。本课题拟建立咬合支持丧失、慢性脑缺血及两者叠加动物模型，检测咬合、血管因素及二者叠加对脑内NO等促炎因子、胶质细胞网、神经元细胞退变及胶质细胞网以NF-κB/iNOS和p38 MAPK/iNOS为主的相关信号通路活化情况的影响；并采用体外细胞共培养技术明确上述因素激活胶质细胞网-NO-神经元退变级联的关键分子及调控通路；最后通过分子及通路阻断动物实验验证。旨在揭示咬合支持丧失通过胶质细胞网促进神经元退变的作用机制，为咬合功能影响脑功能的生物学机制提供理论依据和老年痴呆等脑血管疾病的临床预防策略提供实验证据。

More and more studies confirm occlusal support loss as a risk factor for cognitive impairment in the aging population, but the mechanism is not very clear. Our previous study proved that occlusal support loss with chronic cerebral ischemiaaggravated cognitive impairment, which nitric oxide (NO) signaling pathway mediated by the glial cell networkplayed an important role in the pathogenesis. Therefore we put forward a hypothesis: the glial cell network may be the key pathway for the development of cognitive dysfunction stimulated by loss of occlusal support with cerebral ischemia. Through establishing the animal model of chronic cerebral ischemia and occlusal support loss, we try to find the changes of NO and other pro-inflammatory factor, glial cells, neurons degeneration and functions of NF-κB / iNOS and p38 / MAPK iNOS. In vitro cell co-culture technique was used to identify the key molecules and their regulatory pathways of the activation of glial cell -NO- neurons by the above factors. Through blocking experiments in animal is designed to test the target molecule and cell pathway. Through this study, we will discover neurophysiological mechanisms of cognitive impairment and occlusal support loss, reveal the biological mechanisms of effect of chewing movement on the function of brain, and provide the useful information for improving the life quality in old people.