Astrocytes in Neurofluid Drainage and Brain Disorders: Mechanisms and Therapeutic Implications

Over the past decade, increasing attention has been paid to neurofluid (NF) drainage in the brain, particularly to the glymphatic system and intramural periarterial drainage (IPAD) pathway, which are responsible for substance transport in the brain and are highly dependent on astrocyte function. The dysfunction of these drainage pathways can lead to the accumulation of toxic substances and fluids, and contribute to various brain diseases, such as stroke and Alzheimer's disease. Since astrocytes in the brain closely connect to the microvascular system with their endfeet, in this work, the roles of astrocytes in regulating the glymphatic system and IPAD pathway and their dysfunction in neurodegenerative diseases have been comprehensively reviewed. Additionally, the effects of aquaporin 4, a water channel protein located on astrocytic endfeet, on these two pathways are explored. Furthermore, the possible therapeutic strategies for brain diseases targeting the NF drainage systems have also been proposed and thoroughly discussed.