Transport across the choroid plexus epithelium

Abstract

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development,) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy.

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…The functions of the CSF are, therefore, multiple. They include the overall drainage of brain metabolites diffusing into the CSF, inorganic ion osmoregulation, and pH buffering for the brain extracellular fluid [108]. They also include a role in volume transmission of different biologically active compounds and micronutrients within the brain, a function that is particularly relevant to brain development.…”

“…The current model of CSF secretion is described in [47,108]. A unidirectional active transcellular blood-to-CSF flux of Na + , Cl − , and HCO 3 − creates an osmotic gradient followed by water movement.…”

“…A large number of channels and transporters for monovalent inorganic ions, and aquaporin-1 participate in the secretory process. A number of issues relative to the mechanisms of CSF secretion remain, however, unresolved, among them the potential implication of the poreforming claudin-2 either in CSF-to-blood paracellular K + transfer, or as a water channel ( [108], and see below).…”

Challenges for intraventricular hemorrhage research and emerging therapeutic targets

“…The choroid plexuses are responsible for the majority of CSF secretion 62, 63 and reducing that secretion is a target for IVH therapy and particularly for ameliorating PHH. The choroid plexus is a secretory epithelium where the epithelial cells are linked by tight junctions and contain a wide array of ion transporters as well as water channels (primarily aquaporin 1, AQP1).…”

“…The choroid plexus is a secretory epithelium where the epithelial cells are linked by tight junctions and contain a wide array of ion transporters as well as water channels (primarily aquaporin 1, AQP1). The epithelium is involved in vectoral ion transport that can drive water transport 62 . Clinically, a combination of acetazolamide (a carbonic anhydrase inhibitor) and furosemide (a Na/Cl cotransport inhibitor) has been evaluated as a method of reducing CSF secretion but it doesn’t reduce the need for shunt placement in preterm infants with PHH and actually increased neurological morbidity 5 .…”