Blood-cerebrospinal barrier

Tire brain, which must function in a chemically stable environment, is protected by a tough outer covering, the arachnoid membrane, and by the blood-brain barrier406 407 and the blood-cerebrospinal barrier. Both of these barriers consist of tight junctions similar to those seen in Fig. 1-15A. They are formed between the endothelial cells of the cerebral capillaries and between the epithelial cells that surround the capillaries of the choroid plexus. The choroid plexus consists of capillary beds around portions... 

Specific barriers may serve to limit dmg distribution. The placental barrier is of obvious importance to dmg action in the fetus. Dmg transfers across the placenta primarily by Hpid solubiHty. Hence, this barrier is not particularly restrictive. Similarly, the Hpid solubiHty of a dmg is a primary deterrninant in access to the brain and cerebrospinal fluid. Generally, hydrophilic or charged dmgs can also penetrate to these latter areas, but the result is slow and incomplete. The blood brain barrier is composed of cells having tight junctions which are much less permeable to solutes than are the endotheHal cells of other tissues. 

The area postrema is a circumventricular brain region positioned on the dorsal surface of the medulla on the floor of the fourth ventricle. The blood-brain barrier and the cerebrospinal fluid-brain barrier are absent in this region and consequently many substances that do not pass across capillaries in other regions of the brain can do so in the area postrema. The chemoreceptor trigger zone (CTZ), located in the lateral area postrema is sensitive to blood-borne emetogens. Nerves from the CTZ connect with the vomiting centre. 

The CTZ, located outside the blood-brain barrier (BBB), is exposed to cerebrospinal fluid and blood.2,3 Therefore it is easily stimulated by uremia, acidosis, and the circulation of toxins such as chemotherapeutic agents. The CTZ has many serotonin type 3 (5-HT3), neurokinin-1 (NKj), and dopamine (D2) receptors.2 Visceral vagal nerve fibers are rich in 5-HT3 receptors. They respond to gastrointestinal distention, mucosal irritation, and infection. 

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. 

Tumani, H., et al. (1998). Beta-trace protein in cerebrospinal fluid a blood-CSF barrier-related evaluation in neurological diseases. Ann. Neurol. 44, 882-9. 

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... 

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. 

Two major barrier systems separate the central nervous system from the circulation the BBB and the blood-cerebrospinal fluid barrier (B-CSF-B). These barriers have distinct morphological and physiological characteristics, according to their different tasks. Figure 2.1 highlights the salient features of both barrier systems. 

Variable penetration into cerebrospinal fluid (CSF) has been observed. Disease-related defects in the blood-brain barrier may be responsible for the variations seen. 

The steady-state volume of distribution following IV administration of a 1.5 mg dose averaged 0.534 L/kg. Cerebrospinal fluid obtained from 9 patients at 2 to 3.5 hours following 0.06 or 0.09 mg/kg IV infusion showed measurable concentrations of zalcitabine. The CSFiplasma concentration ratio ranged from 9% to 37% (mean, 20%), demonstrating drug penetration through the blood-brain barrier. 

Although the examination of total protein in cerebrospinal fluid is quite valuable, it is necessary to mention that this parameter does not provide exact information on the function of the blood-CSF barrier. This is easy to understand. The increased concentration of total protein in cerebrospinal fluid can be based both on the failure of the barrier with a subsequent increase in the concentration of albumin and of other proteins originating from serum and on a more significant intrathecal synthesis of immunoglobulins, especially in levels of IgG. 

The albumin quotient is the most precise, routinely used criterion for assessment of the function of the blood-CSF barrier because albumin in cerebrospinal fluid originates exclusively from serum. Its parallel determination during the monitoring of any CSF protein is necessary because this is the only way to differentiate its increased concentration in cerebrospinal fluid due to passive penetration of the respective serum protein from a more specific increase in the concentration of the monitored protein. It is based on its intrathecal synthesis or on a specific transport mechanism for the given protein across the blood-CSF barrier. Unfortunately, some clinicians disregard this recommendation, and this elementary fact is not sufficiently emphasized in publications on cerebrospinal fluid (A22). 

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