The interface between the walls of capillaries and the surrounding tissue is important throughout the body, as it keeps vascular and extravascular concentrations of ions and molecules at appropriate levels. In the brain, the interface is especially crucial.

The special properties of the blood-brain barrier were first observed by Paul Ehrlich in the 1800s. He noted that intravenously injected dyes leaked out of capillaries in most regions of the body to stain the surrounding tissues; the brain, however, remained unstained. His student, Edwin Goldmann, showed that such dyes do not traverse the brain capillary walls.

The restriction of large molecules to the vascular space is the result of tight junctions between neighboring capillary endothelial cells in the brain. Such junctions are not found in capillaries elsewhere in the body, where the spaces between adjacent endothelial cells allow much more ionic and molecular passage. Substances that traverse the walls of brain capillaries must move through the endothelial cell membranes. Therefore, molecular entry into the brain should therefore be determined by solubility in lipids (the major constituent of cell membranes). However, many ions and molecules not soluble in lipids do pass the barrier -- for example, glucose. This happens by means of specific transporters for glucose and other critical molecules and ions.

In addition to tight junctions, astrocytic "end feet" (the terminal regions of astrocytic processes) surround the outside of capillary endothelial cells.

The brain must be carefully shielded from variations in its chemistry and from toxins. It presents a significant problem for the delivery of drugs to the brain.

Neuroscience, Sinaur Associates (QP355.2.N487 1997)

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