Meningeal lymphatic drainage: novel insights into central nervous system disease

Abstract In recent years, increasing evidence has suggested that meningeal lymphatic drainage plays a significant role in central nervous system (CNS) diseases. Studies have indicated that CNS diseases and conditions associated with meningeal lymphatic drainage dysfunction include neurodegenerative diseases, stroke, infections, traumatic brain injury, tumors, functional cranial disorders, and hydrocephalus. However, the understanding of the regulatory and damage mechanisms of meningeal lymphatics under physiological and pathological conditions is currently limited. Given the importance of a profound understanding of the interplay between meningeal lymphatic drainage and CNS diseases, this review covers seven key aspects: the development and structure of meningeal lymphatic vessels, methods for observing meningeal lymphatics, the function of meningeal lymphatics, the molecular mechanisms of meningeal lymphatic injury, the relationships between meningeal lymphatic vessels and CNS diseases, potential regulatory mechanisms of meningeal lymphatics, and conclusions and outstanding questions. We will explore the relationship between the development, structure, and function of meningeal lymphatics, review current methods for observing meningeal lymphatic vessels in both animal models and humans, and identify unresolved key points in meningeal lymphatic research. The aim of this review is to provide new directions for future research and therapeutic strategies targeting meningeal lymphatics by critically analyzing recent advancements in the field, identifying gaps in current knowledge, and proposing innovative approaches to address these gaps.