The glymphatic system and sleep: functional relevance for brain homeostasis and beyond

It has been less than 15 years since the glymphatic system was identified. The discovery has revolutionized the understanding of the unique functions of cerebrospinal fluid (CSF) and the extracellular fluid within the central nervous system (CNS) and their unique connectivity to the rest of the body. The role of sleep in regulating glymphatic clearance from the brain and the potential reciprocal role of the glymphatic system in modulating regional neuronal activities, including sleep states, is rapidly emerging. It is shedding light on the role of sleep and the glymphatic system as toxic waste clearance facilitators for the brain, revealing their synergistic roles in preserving cognitive function and their protective activity in the context of neurodegenerative diseases and aging.