Choroid plexuses (CPs) are localized in the ventricular system of the brain and form one of the interfaces between the blood and the central nervous system (CNS). They are composed of a tight epithelium responsible for cerebrospinal fluid secretion, which encloses a loose connective core containing permeable capillaries and cells of the lymphoid lineage. In accordance with its peculiar localization between 2 circulating fluid compartments, the CP epithelium is involved in numerous exchange processes that either supply the brain with nutrients and hormones, or clear deleterious compounds and metabolites from the brain. Choroid plexuses also participate in neurohumoral brain modulation and neuroimmune interactions, thereby contributing greatly in maintaining brain homeostasis. Besides these physiological functions, the implication of choroid plexuses in pathological processes is increasingly documented. In this review, we focus on some of the novel aspects of CP functions in relation to brain development, transfer of neuro-humoral information, brain/immune system interactions, brain aging, and cerebral pharmaco-toxicology.

Brain homeostasis depends on the composition of both brain interstitial fluid and CSF. Whereas the former is largely controlled by the blood-brain barrier, the latter is regulated by a highly specialized blood-CSF interface, the choroid plexus epithelium, which acts either by controlling the influx of blood-borne compounds, or by clearing deleterious molecules and metabolites from CSF. To investigate mechanisms of brain protection at the choroid plexus, the blood-CSF barrier was reconstituted in vitro by culturing epithelial cells isolated from newborn rat choroid plexuses of either the fourth or the lateral ventricle. The cells grown in primary culture on semipermeable membranes established a pure polarized monolayer displaying structural and functional barrier features, (tight junctions, high electric resistance, low permeability to paracellular markers) and maintaining tissue-specific markers (transthyretin) and specific transporters for micronutriments (amino acids, nucleosides). In particular, the high enzymatic drug metabolism capacity of choroid plexus was preserved in the in vitro blood-CSF interface. Using this model, we demonstrated that choroid plexuses can act as an absolute blood-CSF barrier toward 1-naphthol, a cytotoxic, lipophilic model compound, by a coupled metabolism-efflux mechanism. This compound was metabolized in situ via uridine diphosphate glururonosyltransferase-catalyzed conjugation, and the cellular efflux of the glucurono-conjugate was mediated by a transporter predominantly located at the basolateral, i.e., blood-facing membrane. The transport process was temperature-dependent, probenecid-sensitive, and recognized other glucuronides. Efflux of 1-naphthol metabolite was inhibited by intracellular glutathione S-conjugates. This metabolism-polarized efflux process adds a new facet to the understanding of the protective functions of choroid plexuses.

In Alzheimer's disease, the neuritic or senile amyloid plaques in hippocampus and association cortex, the diffuse plaques in brain areas such as the cerebellum and sensorimotor cortex, and the amyloid deposits in the walls of pial and parenchymal blood vessels are mainly composed of amyloid β‐peptides. In the present study, either soluble 40‐residue amyloid β‐peptide radiolabeled with 125I (I‐sAβ) or [14C]polyethylene glycol ([14C]‐PEG, a reference material) was briefly infused into one lateral ventricle of normal rats. By 3.5 min, 30% of the I‐sAβ was cleared from ventricular CSF into blood; another 30% was removed over the next 6.5 min. No [14C]PEG was lost from the CSF‐brain system during the first 5 min, and only 20% was cleared by 10 min. Much of the I‐sAβ that reached the subarachnoid space was retained by pial arteries and arterioles. Virtually no I‐sAβ was found in brain. The clearance of amyloid β‐peptides from the CSF‐brain system, reported herein for normal rats, may be reduced in Alzheimer's disease, thus contributing to amyloid deposition in cerebral tissue and blood vessels.

The brain, with the exception of the choroid plexuses and Circumventricular organs, is partially protected from the invasion of blood‐borne chemicals by the specific morphological properties of the cerebral micro‐vessels, namely, the tight junctions of the blood‐brain barrier. Recently, several enzymes that are primarily involved in hepatic drug metabolism have been shown to exist in the brain, albeit at relatively low specific activities. In the present study, the hypothesis that these enzymes are located primarily at blood‐brain interfaces, where they form an “enzymatic barrier,” is tested. By using microdissection techniques or a gradient‐centrifugation isolation procedure, the activities of seven drug‐metabolizing enzymes in isolated microvessels, choroid plexuses, meningeal membranes, and tissue from three Circumventricular organs (the neural lobe of the hypophysis, pineal gland, and median eminence) were assayed. With two exceptions, the activities of these enzymes were higher in the three Circumventricular organs and cerebral microvessel than in the cortex. Very high membrane‐bound epoxide hydrolase and UDP‐glucuronosyltransferase activities (approaching those in liver) and somewhat high 7‐benzoxyre‐sorufin‐O‐dealkylase and NADPH‐cytochrome P‐450 reductase activities were determined in the choroid plexuses. The pia‐arachnoid membranes, but not the dura matter, displayed drug‐metabolizing enzyme activities, notably that of epoxide hydrolase: The drug‐metabolizing enzymes located at these nonparenchymal sites may function to protect brain tissue from harmful compounds.