The glymphatic system in cerebrospinal fluid dynamics – clinical implications, its evaluation, and application to therapeutics

BACKGROUND: The glymphatic system is a waste clearance system that facilitates the efficient removal of interstitial solutes, including neurotoxic substances such as β-amyloid, from the central nervous system. Numerous studies have highlighted its pivotal role in the pathophysiology of neurodegenerative diseases and cerebrospinal fluid (CSF) disorders. A comprehensive understanding and accurate evaluation of the glymphatic system are of significant clinical importance. Furthermore, emerging evidence suggests that modulating glymphatic activity holds therapeutic potential, including enhancing drug delivery across the brain. SUMMARY: This review consolidates current insights into the glymphatic system, addressing areas of consensus as well as ongoing controversies. The relationship between glymphatic dysfunction and CSF disorders is discussed, alongside advancements in evaluation methodologies. Additionally, therapeutic applications of glymphatic modulation are summarized, particularly its role in optimizing drug distribution within the brain. KEY MESSAGES: This review provides a comprehensive overview of the current knowledge on the glymphatic system and highlights imaging techniques used to assess human glymphatic function, including magnetic resonance imaging (MRI) with contrast agents, diffusion tensor imaging, and emerging techniques such as MRI with 17O-labeled water. Furthermore, the therapeutic implications of glymphatic modulation are discussed, and directions for future research are proposed.