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Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity
https://orcid.org/0000-0002-6627-064X
AbstractWhite matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. 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‐associated virus delivery of vascular endothelial growth factor‐C (VEGF‐C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF‐C 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.
Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity
https://orcid.org/0000-0002-6627-064X
AbstractWhite matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. 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‐associated virus delivery of vascular endothelial growth factor‐C (VEGF‐C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF‐C 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.
Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity
https://orcid.org/0000-0002-6627-064X
AbstractWhite matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. 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‐associated virus delivery of vascular endothelial growth factor‐C (VEGF‐C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF‐C 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.
Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity
Advanced Science
Zhou, Ying (Autor:in) / Xue, Rui (Autor:in) / Li, Yifei (Autor:in) / Ran, Wang (Autor:in) / Chen, Yuping (Autor:in) / Luo, Zhongyu (Autor:in) / Zhang, Kemeng (Autor:in) / Zhang, Ruoxia (Autor:in) / Wang, Junjun (Autor:in) / Fang, Mengmeng (Autor:in)
Advanced Science ; 11
01.07.2024
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity
| Wiley | 2024
| Wiley | 2024
| Wiley | 2025
British Library Online Contents | 2013
| British Library Conference Proceedings | 1988