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contributor to VCI. Several potential physiopathologic mechanisms have been proven to be involved in the process of CSVD, such as blood-brain barrier damage, small vessels stiffening, venous collagenosis, cerebral blood flow reduction, white matter rarefaction, chronic ischaemia, neuroinflammation, myelin damage, and subsequent neurodegeneration. However, there still is a limited overall understanding of the sequence and the relative importance of these mechanisms. The glymphatic system (GS) and meningeal lymphatic vessels (mLVs) are the analogs of the lymphatic system in the central nervous system (CNS). As such, these systems play critical roles in regulating cerebrospinal fluid (CSF) and interstitial fluid (ISF) transport, waste clearance, and, potentially, neuroinflammation. Accumulating evidence has suggested that the glymphatic and meningeal lymphatic vessels played vital roles in animal models of CSVD and patients with CSVD. Given the complexity of CSVD, it was significant to understand the underlying interaction between glymphatic and meningeal lymphatic transport with CSVD. Here, we provide a novel framework based on new advances in main four aspects, including vascular risk factors, potential mechanisms, clinical subtypes, and cognition, which aims to explain how the glymphatic system and meningeal lymphatic vessels contribute to the progression of CSVD and proposes a comprehensive insight into the novel therapeutic strategy of CSVD.<\/jats:p>","DOI":"10.3390\/biom12060748","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T08:50:22Z","timestamp":1653555022000},"page":"748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Yu","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Chinese Institute for Brain Research, Beijing 102206, China"},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing 100070, China"},{"name":"Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100070, China"},{"name":"National Center for Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Chinese Institute for Brain Research, Beijing 102206, China"},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing 100070, China"},{"name":"Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100070, China"},{"name":"National Center for Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5363-8898","authenticated-orcid":false,"given":"Yiyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Chinese Institute for Brain Research, Beijing 102206, China"},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing 100070, China"},{"name":"Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100070, China"},{"name":"National Center for Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Chinese Institute for Brain Research, Beijing 102206, China"},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing 100070, China"},{"name":"Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100070, China"},{"name":"National Center for Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3267-0039","authenticated-orcid":false,"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Chinese Institute for Brain Research, Beijing 102206, China"},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing 100070, China"},{"name":"Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100070, China"},{"name":"National Center for Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nam, K., Kwon, H., Lim, J., Han, M., Nam, H., and Lee, Y. 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