Cerebrospinal fluid choroid plexus barrier

Rao, V. V., Dahlheimer, J. L., Bardgett, M. E., et al. (1999) Choroid plexus epithelial expression of MDRl P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc. Natl. Acad. Sci. U. S. A. 96, 3900-3905. 

Embedded within the brain are four ventricles or chambers that form a continuous fluid-filled system. In the roof of each of these ventricles is a network of capillaries referred to as the choroid plexus. It is from the choroid plexuses of the two lateral ventricles (one in each cerebral hemisphere) that cerebrospinal fluid (CSF) is primarily derived. Due to the presence of the blood-brain barrier, the selective transport processes of the choroid plexus determine the composition of the CSF. Therefore, the composition of the CSF is markedly different from the composition of the plasma. However, the CSF is in equilibrium with the interstitial fluid of the brain and contributes to the maintenance of a consistent chemical environment for neurons, which serves to optimize their function. 

Wijnholds J, deLange EC, Scheffer GL, van den Berg DJ, Mol CA, van d, V et al. Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J Clin Invest 2000 105(3)779-285. 

Fig. 15.1 D iagram showing a longitudinal cross-section of the blood-cerebrospinal fluid barrier at the choroid plexus. This barrier is formed by epithelial or choroid cells held together at their apices by tight junctions. The...

The exit of drugs from the CNS can involve (1) diffusion across the blood-brain barrier in the reverse direction at rates determined by the lipid solubility and degree of ionization of the drug, (2) drainage from the cerebrospinal fluid (CSP) into the dural blood sinuses by flowing through the wide channels of the arachnoid villi, and (2) active transport of certain organic anions and cations from the CSF to blood across the choroid plexuses... 

In addition, the epithelial cells of the choroid plexus facing the cerebrospinal fluid (CSF) constitute the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is also a significant area for exchange between the blood and the CSF. In rats the total calculated surface area of the choroid plexus is about 33% of that of the BBB [2]. In humans, based on the relative mass of the choroid plexus in comparison with the brain, the relative surface area of the choroid plexus may be in the region of 10% of that of the BBB. The CSF is secreted across the choroid plexus epithelial cells into the brain ventricular system [3] the remainder of the brain extracellular fluid (ECF) and the interstitial fluid (ISF) are secreted at the capillaries of the BBB themselves [4]. The ratio of fluid production from these sites is 40% 60%, respectively [5],... 

Shu C, Shen H, Teuscher NS, Lorenzi PJ, Keep RF, Smith DE. Role of PEPT2 in pep tide/mimetic trafficking at the blood-cerebrospinal fluid barrier studies in rat choroid plexus epithelial cells in primary culture. J Pharmacol Exp Ther 2002 301 820-829. 

The choroid plexus are bags composed of epithelial cells that project into the ventricles and contain a capillary plexus (lohanson, 1988). The capillaries do not have barrier function and so produce an ultrafiltrate, w hich fills the bag. The epithelial cells have tight junctions and so prevent the ultrafiltrate fi om entering the ventricular space. Unlike the capillaries, the epithelial cells of the choroid plexus have a high rate of vesicular turnover, w hich is responsible for the production of the cerebrospinal fluid (CSF). How ever, the CSF is not an ultra-filfi ate, but a secreted substance. The choroid plexus also has many selective transport systems, some of w hich are specific to it or are enriched in comparison to the vascular BBB. 

The second barrier separating the central nervous system from blood circulation is the choroid plexus or plexus choroideus. It is formed by a vascular sponge, which is surrounded by epithelial cells (ECs) and which is located within the ventricles ofthe brain. The actual barrier is formed by the epithelial cells and not by the interior capillary. One of the major functions of the choroid plexus is the production of cerebrospinal fluid (liquor). In addition, the epithelial cells secrete ions, peptides, nutrients, and vitamins [105]. 

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BGB) at the choroid plexus are two major barriers between the GNS and blood (Figure 7.11). The BBB, however, has the most extensive surface area approximately 1000 times that of the choroid plexus, which makes it the primary route for drug access to the brain. Furthermore, the high perfusion rate of the BBB allows lipophilic drug concentrations to equilibrate rapidly between the blood and brain. 

Orally ingested salicylates are absorbed rapidly, predominantly from the upper small intestine. Appreciable concentrations are found in plasma in less than 30 minutes after a single dose, a peak value is reached in -1 hour and then declines gradually. After absorption, salicylates are distributed throughout most body tissues and transcellular fluids, primarily by pH-dependent passive processes. Salicylates are transported actively by a low-capacity, saturable system out of the cerebrospinal fluid (CSF) across the choroid plexus. The drugs readily cross the placental barrier. 

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