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Chronic unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful events. Western blotting and coimmunoprecipitation were used to provide mechanistic insights. We demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex, cerebellum, hippocampus, midbrain, and brainstem. Furthermore, we showed that deep brain lymphatic vessels can be regulated by stressful life events. Chronic stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the amygdala. No changes were observed in prefrontal cortex, lateral habenula, or dorsal raphe nucleus. Chronic corticosterone treatment reduced lymphatic endothelial cell markers in the hippocampus. Mechanistically, chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization mechanisms. Our results provide new insights into the characteristic features of deep brain lymphatic vessels, as well as their regulation by stressful life events.<\/jats:p>","DOI":"10.34133\/research.0120","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T09:23:32Z","timestamp":1679995412000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":21,"title":["Characteristic Features of Deep Brain Lymphatic Vessels and Their Regulation by Chronic Stress"],"prefix":"10.34133","volume":"6","author":[{"given":"Junzhuang","family":"Chang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, \rFudan University, Shanghai 200032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingqing","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, \rFudan University, Shanghai 200032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, \rFudan University, Shanghai 200032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, \rFudan University, Shanghai 200032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences; Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Institute of Acupuncture and Moxibustion, Fudan Institutes of Integrative Medicine, \rFudan University, Shanghai 200032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences; Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Institute of Acupuncture and Moxibustion, Fudan Institutes of Integrative Medicine, \rFudan University, Shanghai 200032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nashat","family":"Abumaria","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, \rFudan University, Shanghai 200032, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"issue":"6500","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","DOI":"10.1126\/science.aax4063","article-title":"Biological functions of lymphatic vessels","volume":"369","author":"Petrova TV","year":"2020","unstructured":"Petrova TV, Koh GY. 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