Blood-brain barrier: a definition of normal and altered function.

The anatomical component of the blood-brain barrier (BBB) has been shown to be the cerebral capillary. These capillary endothelial cells are connected by continuous tight intercellular junctions and under normal conditions do not demonstrate transendothelial channels or pinocytotic vesicles. The rate that substances penetrate the BBB is related to molecular size, lipid solubility, and the presence of a specific carrier-mediated transport system. This latter mechanism for transendothelial passage is utilized for the movement of a wide variety of biologically important compounds such as sugars, amino acids, and organic acids. In certain pathological conditions, the permeability of the BBB is altered so that normally excluded plasma proteins and fluid enter the brain extracellular space, with the subsequent development of cerebral edema. In other abnormal conditions, alterations in the specialized transport systems operating across the cerebral capillary result in adverse changes in cerebral and neurotransmitter metabolism. An understanding of the unique properties of the BBB and of the changes that occur in pathological conditions has allowed the development of rational therapeutic strategies for a wide variety of diseases of the central nervous system.