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Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno\u2010associated virus delivery of vascular endothelial growth factor\u2010C (VEGF\u2010C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF\u2010C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.<\/jats:p>","DOI":"10.1002\/advs.202402059","type":"journal-article","created":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T06:53:16Z","timestamp":1714891996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity"],"prefix":"10.1002","volume":"11","author":[{"given":"Ying","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Neurology the Second Affiliated Hospital 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