Figure 1. Schematic of CSF production and circulation in the brain.

Cerebrospinal fluid (CSF) is formed in the choroid plexuses in the 3^rd (3V), 4^th (4V) and lateral ventricles (LV, Bottom Right), then exits into the subarachnoid space (SAS) at the cisterna magna. Classically, CSF is cleared by bulk reabsorption into the bloodstream via arachnoid villi or by clearance to peripheral lymphatic vessels accessed along cranial nerve sheathes. More recent research suggests that from the SAS, a portion of the CSF circulates into the parenchyma of the brain along perivascular spaces (PVS) surrounding penetrating arteries, exchanging with surrounding brain interstitial fluid (ISF, Top Right). ISF and its associated solutes and wastes are in turn cleared along PVSs surrounding large caliber draining veins. This processes is supported by astroglial water transport through the aquaporin-4 (AQP4) water channel, which is localized to the perivascular astrocytic endfeet that surround the cerebral vasculature (Bottom Left). Interstitial solutes are cleared along peri-venous spaces into cisternal CSF spaces, where they have access to sinus-associated lymphatic vessels (Top Left). Abbreviations: Astrocyte (AST), basement membrane (BM), epithelial cells (EpC), pia mater (PM), smooth muscle cell (VSM), sigmoid sinus (SmS), superior saggital sinus (SSS), transverse sinus (TS). Adapted from [129].