Fluid and Waste Clearance in Central Nervous System Health and Diseases

Background: In respect to the circulatory system, the central nervous system (CNS) differs from other organs in the body by three main features. First, the CNS is surrounded by a compartment filled with cerebrospinal fluid (CSF). Second, the CNS is devoid of lymphatic vessels, which are found in the dura mater of the meninges. Third, the CNS blood vasculature serves as a scaffold to perivascular spaces allowing CSF to circulate into the CNS parenchyma via the glymphatic system. Summary: This review highlights the contribution of the glymphatic system and meningeal lymphatic vasculature to CNS homeostasis and also recapitulates the alterations of glymphatic-meningeal lymphatic systems that have been associated to neurological disorders, especially neurodegenerative diseases. Key Message: We discuss the controversies and limitations in current research, emphasizing the need for cautious interpretation while highlighting the potential of glymphatic and meningeal lymphatic pathways as therapeutic targets in neurological disorders.