Studies on the human choroid plexus in vitro

A constant and well-controlled composition of extracellular fluid in the central nervous system (CNS) is essential for neuronal processing. Thus, all existing vertebrates have cellular structures that provide efficient physical separation of the circulating plasma from brain extracellular fluids [1]. The two most important are the endothelial blood–brain barrier (BBB) which separates plasma from the interstitial fluid of the brain, and the epithelial blood-cerebrospinal fluid barrier (BCSFB), which separates blood from ventricular cerebrospinal fluid (CSF). These cellular structures impede free paracellular diffusion of hydrophilic solutes and transcellular diffusion of lipophilic compounds from circulating plasma into extracellular fluids of the brain and exclude xenobiotics, providing the controlled environment required for optimal CNS function.The BCSFB is formed by the epithelium of the choroid plexuses (CPs). The BCSFB has a considerable surface area for exchange between the blood and the CSF through the presence of microvilli on the apical surface and interdigitations on the basolateral surface. The barrier phenotype of this cellular interface is achieved mainly by continuous tight junctions (TJs) between adjacent cells of the CP epithelium (CPE). These intercellular structures greatly limit paracellular diffusion and, thus, exchange of polar solutes between the blood and the CSF [2]. Claudins 1, 2, 3 and 11 are the most important members of the claudin family of TJ proteins of the CPE [3]. Claudin 11 in the TJs of the CPE is responsible for parallel-stranded TJs, observed in freeze-fracture morphology [3,4]. This relationship between structure and molecular composition of the TJs is important and could be used as an indicator of whether or not the CPE maintains functional features in vitro. Together with restriction of free paracellular diffusion, the presence of a large number of transport systems and intracellular metabolic activities contribute significant