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Targeting Meningeal Lymphatic Vessels to Advance Stroke Therapy
Yang Liu1,2, Xiansheng Liu3,4, Shihao Lin3
1Department of Neurology, Tongren City People's Hospital, Tongren, Guizhou, China.
Abstract:
Meningeal lymphatic vessels (mLVs) have recently emerged as pivotal regulators of central nervous system homeostasis, orchestrating cerebrospinal fluid (CSF) drainage, metabolic waste clearance, and neuroimmune surveillance at the brain and meningeal interface. Stroke, ischemic or hemorrhagic, exerts profound functional insults on mLVs, disrupting clearance pathways. These disturbances not only exacerbate acute edema and neuroinflammation but also dictate long-term outcomes, including post-stroke cognitive decline. In this review, we synthesize current understanding of mLVs anatomy and physiology, emphasizing their dynamic remodeling after stroke. We further examine the context-dependent immune functions of mLVs, and their role in shaping post-stroke brain injury and repair. In addition, we discuss emerging therapeutic strategies targeting the glymphatic-lymphatic axis and outline key translational challenges. Although these findings support a framework in which impaired fluid clearance contributes to stroke pathophysiology, most mechanistic insights derive from preclinical models, and direct evidence in human stroke remains limited. Accordingly, therapeutic implications should be interpreted with caution and require rigorous clinical validation.
Insights
Meningeal lymphatic vessels (mLVs) are crucial for brain health. Stroke impairs mLVs, worsening brain injury and cognitive decline, highlighting potential therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Meningeal lymphatic vessels (mLVs) are key to central nervous system (CNS) homeostasis, managing cerebrospinal fluid (CSF) drainage, waste clearance, and immune surveillance.
- Stroke significantly disrupts mLV function, exacerbating edema and neuroinflammation, and contributing to long-term cognitive deficits.
Purpose of the Study:
- To review the anatomy, physiology, and dynamic remodeling of mLVs post-stroke.
- To examine the immune roles of mLVs in brain injury and repair after stroke.
- To discuss therapeutic strategies targeting the glymphatic-lymphatic axis for stroke treatment.
Main Methods:
- Literature review synthesizing current understanding of mLVs in stroke.
- Analysis of preclinical models and available human data on mLV function after stroke.
Main Results:
- mLVs undergo significant remodeling following stroke, impairing crucial clearance pathways.
- Dysfunctional mLVs contribute to acute brain injury and chronic post-stroke cognitive impairment.
- Emerging therapies targeting the glymphatic-lymphatic axis show promise but require clinical validation.
Conclusions:
- Impaired mLV function is implicated in stroke pathophysiology, affecting fluid clearance and brain repair.
- Current mechanistic insights are largely from preclinical studies, necessitating caution in clinical application.
- Further research and rigorous clinical validation are essential for translating findings into effective stroke therapies.
