Dataset Information

Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

ABSTRACT: White 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.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC11234435 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

Zhou Ying Y Xue Rui R Li Yifei Y Ran Wang W Chen Yuping Y Luo Zhongyu Z Zhang Kemeng K Zhang Ruoxia R Wang Junjun J Fang Mengmeng M Chen Cong C Lou Min M

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240505 26

White 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 lymphangio ...[more]

PMID: 38704728

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Project description:BackgroundWhite matter hyperintensity (WMH) is one of the typical neuroimaging manifestations of cerebral small vessel disease (CSVD), and the WMH correlates closely to cognitive impairment (CI). CSVD patients with WMH own altered topological properties of brain functional network, which is a possible mechanism that leads to CI. This study aims to identify differences in the characteristics of some brain functional network among patients with different grades of WMH and estimates the correlations between these different brain functional network characteristics and cognitive assessment scores.Methods110 CSVD patients underwent 3.0 T Magnetic resonance imaging scans and neuropsychological cognitive assessments. WMH of each participant was graded on the basis of Fazekas grade scale and was divided into two groups: (A) WMH score of 1-2 points (n = 64), (B) WMH score of 3-6 points (n = 46). Topological indexes of brain functional network were analyzed using graph-theoretical method. T-test and Mann-Whitney U test was used to compare the differences in topological properties of brain functional network between groups. Partial correlation analysis was applied to explore the relationship between different topological properties of brain functional networks and overall cognitive function.ResultsPatients with high WMH scores exhibited decreased clustering coefficient values, global and local network efficiency along with increased shortest path length on whole brain level as well as decreased nodal efficiency in some brain regions on nodal level (p < 0.05). Nodal efficiency in the left lingual gyrus was significantly positively correlated with patients' total Montreal Cognitive Assessment (MoCA) scores (p < 0.05). No significant difference was found between two groups on the aspect of total MoCA and Mini-mental State Examination (MMSE) scores (p > 0.05).ConclusionTherefore, we come to conclusions that patients with high WMH scores showed less optimized small-world networks compared to patients with low WMH scores. Global and local network efficiency on the whole-brain level, as well as nodal efficiency in certain brain regions on the nodal level, can be viewed as markers to reflect the course of WMH.

Dataset Information

Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

Publications

Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

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