The glymphatic system and meningeal lymphatic vessels: from physiology to pathophysiology, with insights into...

The lymphatic system plays critical roles in immune defense, fluid homeostasis, substance metabolism, and cellular communication. Traditionally, it was believed that the vertebrate brain lacked a classical lymphatic system. Studies have revealed the presence of the glymphatic system (GS) and meningeal lymphatic vessels (MLVs), which are thought to play important roles in regulating material transport and immune processes within the central nervous system (CNS), in ways that resemble aspects of the peripheral lymphatic system. Emerging evidence suggests that CNS homeostasis may be influenced by the proper function of GS and MLVs, and that their dysfunction could contribute to the accumulation of toxic substances in the brain, thereby potentially increasing the risk of certain CNS disorders. This review provides a systematic overview of the basic structure, physiological functions, and imaging approaches related to GS and MLVs. We summarize current evidence regarding how GS and MLVs may be influenced by physiological factors such as hemodynamics, sleep, and aging. We also outline their potential involvement in the pathophysiology of CNS disorders, including neurodegenerative diseases, neuroinflammatory conditions, and brain tumors. By highlighting the putative roles of GS and MLVs in disease processes and their possible relevance as therapeutic targets, this review underscores emerging strategies that could be explored for the prevention and management of CNS diseases. At the same time, a more comprehensive understanding of GS and MLVs may provide useful insights into novel interventions aimed at mitigating neurological dysfunction and improving clinical outcomes.