The glymphatic system: A new insight into the understanding of neurological diseases

Abstract The glymphatic system (GS) is a newly discovered transport system in the central nervous system (CNS) that plays a crucial role in maintaining homeostasis by facilitating the clearance of metabolic waste and fluid transport. This groundbreaking discovery has significantly advanced our understanding of CNS physiology. Historically, the brain was thought to lack a lymphatic system, leaving its mechanisms for waste clearance largely enigmatic. This review elaborates on the anatomical structures of the GS, including the perivascular space, aquaporin 4 (AQP4) channels, and the meningeal lymphatic system, as well as their functional dynamics, to elucidate the GS's waste clearance mechanism. It also explores the key factors influencing GS activity, such as sleep, arterial pulsation, aging, and pharmacological interventions. Moreover, it examines the implications of GS dysfunction in various neurological diseases, including stroke, Alzheimer's disease, and Parkinson's disease. Furthermore, it discusses the latest diagnostic and therapeutic strategies targeting this vital system. Understanding the role of the GS in CNS homeostasis not only provides new insights into the pathophysiology of neurological diseases but also opens novel avenues for therapeutic interventions to enhance brain health and mitigate neurodegenerative processes.