Choroid Plexus and Drug Removal Mechanisms.

Timely and efficient removal of xenobiotics and metabolites from the brain is crucial in maintaining the homeostasis and normal function of the brain. The choroid plexus (CP) forms the blood-cerebrospinal fluid barrier and vitally removes drugs and wastes from the brain through several co-existing clearance mechanisms. The CP epithelial (CPE) cells synthesize and secrete the cerebrospinal fluid (CSF). As the CSF passes through the ventricular and subarachnoid spaces and eventually drains into the general circulation, it collects and removes drugs, toxins, and metabolic wastes from the brain. This bulk flow of the CSF serves as a default and non-selective pathway for the removal of solutes and macromolecules from the brain interstitium. Besides clearance by CSF bulk flow, the CPE cells express several multispecific membrane transporters to actively transport substrates from the CSF side into the blood side. In addition, several phase I and II drug-metabolizing enzymes are expressed in the CPE cells, which enzymatically inactivate a broad spectrum of reactive or toxic substances. This review summarizes our current knowledge of the functional characteristics and key contributors to the various clearance pathways in the CP-CSF system, overviewing recent developments in our understanding of CSF flow dynamics and the functional roles of CP uptake and efflux transporters in influencing CSF drug concentrations.