A balanced view of choroid plexus structure and function: Focus on adult humans

Highlights

• Some papers have downplayed the role of the choroid plexus (CP) in CSF production.

• This paper reviews the evidence showing that the CP is the main site of CSF formation.

• The CP also has a pivotal role in controlling CSF composition.

• Drugs and micronutrients in ventricular CSF may penetrate deeply into the brain.

Abstract

Recently tremendous progress has been made in studying choroid plexus (CP) physiology and pathophysiology; and correcting several misconceptions about the CP. Specifically, the details of how CP, a locus of the blood–CSF barrier (BCSFB), secretes and purifies CSF, generates intracranial pressure (ICP), maintains CSF ion homeostasis, and provides micronutrients, proteins and hormones for neuronal and glial development, maintenance and function, are being understood on a molecular level. Unequivocal evidence that the CP secretory epithelium is the predominant supplier of CSF for the ventricles comes from multiple lines: uptake kinetics of tracer ²²Na and ³⁶Cl penetration from blood to CSF, autoradiographic mapping of rapid ²²Na and ³⁶Cl permeation (high permeability coefficients) into the cerebroventricles, CSF sampling from several different in vivo and in vitro CP preparations, CP hyperplasia that increases CSF formation and ICP; and in vitro analysis of CP ability to transport molecules (with expected directionality) and actively secrete fluid against an hydrostatic fluid column. Furthermore, clinical support for this CP–CSF model comes from neurosurgical procedures to remove lateral ventricle CPs in hydrocephalic children to reduce CSF formation, thereby relieving elevated ICP. In terms of micronutrient transport, ascorbic acid, folate and other essential factors are transported by specific (cloned) carriers across CP into ventricular CSF, from which they penetrate across the ependyma and pia mater deeply into the brain to support its viability and function. Without these choroidal functions, severe neurological disease and even death can occur. In terms of efflux or clearance transport, the active carriers (many of which have been cloned and expressed) in the CP basolateral and apical membranes perform regulatory removal of some metabolites (e.g. choline) and certain drugs (e.g. antibiotics like penicillin) from CSF, thus reducing agents such as penicillin to sub-therapeutic levels. Altogether, these multiple transport and secretory functions in CP support CSF homeostasis and fluid dynamics essential for brain function.