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The blood-brain barrier. II. Physiological data
Authors:J M Lefauconnier  J J Hauw
Abstract:In the first part of this review, the morphological characteristics of the interfaces between blood and some compartments of the central nervous system have been described. The blood-brain barrier (BBB) is situated between the blood and the brain extracellular space (ECS) at the endothelial cells of brain capillaries joined by tight junctions. The blood-cerebrospinal fluid (CSF) barrier is mainly situated at the epithelium of the choroid plexuses. In this second part, the general mechanisms and methods of study of the transport of low molecular weight substances across the BBB are reviewed. In addition water and solute transports across the interfaces are described. The third part will deal with the transport of metabolic substrates and of drugs, with the barrier to neurotransmitters and with the physiological alterations of the permeability of the blood-brain barrier. Blood-brain transport is transcellular. According to the nature of the transported molecule it can be either by diffusion through the membranes (lipophilic molecules) or carrier-mediated (hydrophilic molecules such as metabolic substrates). In vivo methods of study have first been experimental. The recent use of short-lived positron-emitting radioisotopes should extent their use to clinical studies. In vitro measurement of transport on isolated capillaries or choroid plexuses give additional information. Water exchange between plasma and the brain is rapid. However, the permeability of the brain capillaries for water is lower than that of other capillaries and of most membranes, but more similar to that of lipid bilayers and of most tight epithelia. The permeability for water of the choroid plexuses which secrete CSF is much higher than that of brain capillaries. CSF and ECS electrolyte composition is under strict homeostatic regulation, leaving it independent of fluctuations in plasma composition. This constant composition is the consequence of the low permeability of brain capillaries to electrolytes as well as that of the presence of a sodium potassium dependent ATPase on the abluminal membrane of capillaries and the apical membrane of choroid plexuses. This enzyme contributes to the extrusion of potassium from the CSF and ECS and allows a large gradient of potassium to be created between ECS and plasma. A low level of potassium in CSF and ECS is in fact needed for normal nerve conduction.
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