脑小血管病认知功能障碍的脑类淋巴-脑膜淋巴管机制研究

脑小血管病（CSVD）是痴呆最重要血管促成因素，且与阿尔茨海默氏病交互，与45%的痴呆有关。申请人前期研究提示CSVD患者存在脑类淋巴功能下降，且脑类淋巴功能与CSVD患者认知功能成正相关。申请人前期已建立鞘内注射钆对比剂的磁共振显示脑类淋巴通路和脑膜淋巴管，及无创多模式磁共振技术评估脑类淋巴-脑膜淋巴管功能。本项目拟在前期研究基础上，通过最新鞘内注射钆对比剂的磁共振技术在小样本CSVD患者中分析脑类淋巴-脑膜淋巴管功能，探究其与CSVD进展和认知功能下降的关系；进而利用无创多模式磁共振技术在大样本CSVD患者中验证脑类淋巴-脑膜淋巴管功能与CSVD进展之间的因果关系，及其对认知功能的影响；最后利用CSVD大鼠模型证实脑类淋巴-脑膜淋巴管功能参与CSVD进展及认知功能下降的机制。有望阐明CSVD认知功能障碍的新机制，拓宽新兴的脑类淋巴-脑膜淋巴管功能研究，并为认知功能障碍的防治提供新靶点。

Cerebral small vessel disease (CSVD) is the most important vascular risk factor of dementia, and interacts with Alzheimer's disease, which is related to 45% of dementia. The applicant's previous study suggested that in CSVD patients, the function of glymphatic pathway decreased and was positively correlated with cognitive function. The applicant has established intrathecal injection of gadolinium contrast agent magnetic resonance technology to visualize the glymphatic pathway and meningeal lymphatic vessels, and non-invasive multi-mode magnetic resonance technology to evaluate the function of glymphatic pathway and meningeal lymphatic vessels. On the basis of previous studies, the applicant intends to analyze the function of glymphatic pathway and meningeal lymphatic vessels in small samples of CSVD patients by the latest intrathecal injection of gadolinium contrast agent magnetic resonance technology, and explore its relationship with the progress of CSVD and cognitive decline. Then the applicant plans to use non-invasive multi-mode magnetic resonance technology to verify the causal link between the progress of CSVD and the dysfunction of glymphatic pathway and meningeal lymphatic vessels, and their impact on cognitive decline in large samples of CSVD patients. Finally, the CSVD rat model will be used to verify whether the function of glymphatic pathway and meningeal lymphatic vessels is involved in the progress of CSVD and the decline of cognitive function. It is expected to elucidate the new mechanism of cognitive dysfunction in CSVD, broaden the new research on the function of glymphatic pathway and meningeal lymphatic vessels, and provide new targets for the prevention and treatment of cognitive dysfunction.