Barrier mechanisms in the brain, I. Adult brain.

1. The adult brain functions within a well-controlled (internal) environment that is separate from that of the internal environment of the rest of the body as a whole. 2. The underlying mechanism of control of the brain's internal environment lies in the presence of tight junctions between the cerebral endothelial cells at the blood-brain interface (blood-brain barrier) and between choroid plexus epithelial cells (blood-cerebrospinal fluid (CSF) barrier). 3. The effect of tight junctions at the blood-brain and blood-CSF barriers is to convert the properties of the individual endothelial and epithelial cells into properties of these interfaces as a whole. 4. Superimposed on the diffusion restriction provided by the tight junctions in the blood-brain and blood-CSF barriers is a series of transport mechanisms into and out of the brain and CSF that determine and control the internal environment of the brain with respect to a wide range of molecules, such as electrolytes, amino acids, glucose, vitamins and peptides. 5. The physical characteristics of drugs, together with their interaction with the properties of the barriers between blood, brain and CSF, determine the extent to which drugs penetrate into the brain. 6. Drugs can be targeted to the brain by making use of knowledge of this interaction between the physical properties of a drug (which can be modified by manipulation of the structure of the molecule in predictable ways) and the influx/efflux mechanisms present in the blood-CSF and blood-brain interfaces.