The Glymphatic System and Brain Interstitial Fluid Homeostasis

This chapter reviews the basis of brain interstitial fluid homeostasis and discusses the roles of the glymphatic system in the clearance of fluid and solutes. The anatomical organization of the glymphatic system and its drainage into cervical and meningeal lymph vessels, as well as the role of astrocytes, the perivascular space, and the sleep-wake cycle in the regulation of interstitial space and bulk flow, are described. The existence of the glymphatic system opens up new ways to understand the mechanisms underlying brain fluid dynamics and acute edema formation following stroke. Influx of cerebrospinal fluid along the perivascular spaces surrounding cerebral arteries and failure of ischemic cells to clear excess interstitial fluid, as well as perivasculitis, likely contribute to cytotoxic and vasogenic brain edema. As such, diagnostic imaging or manipulation of the glymphatic pathway may unlock novel therapeutic opportunities for cerebrovascular disease.