Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier
Fenestrated blood vessels in the rat choroid plexus are permeable to dye-labelled proteins, HRP and ferritin. Most leakage appears to be via fenestrae but some additional escape of marker appears to take place through transient and reversible openings in the junctions between endothelial cells. After they have escaped into the choroidal stroma markers are prevented from entering the CSF by tight junctions between the epithelial cells which cover the choroid plexus, but how they are removed from the extravascular space is not known. Electron microscope study of rats who have been given multiple intravenous injections of ferritin shows that extravascular ferritin is take up both by connective tissue cells in the choroidal stroma and by choroidal epithelial cells. The findings suggest that the ingested protein is subsequently broken down within lysosomal vacuoles in the cytoplasm of these cells. Such intracellular digestion may be the major means of controlling the protein content of the extravascular spaces of the choroid plexus.