Significance of the Blood Brain Barrier

It is likely that the blood-brain barrier serves primarily to preserve the internal environment of the brain and prevent sudden increases in concentration of a variety of water-soluble ionized substances, including many circulating neurotransmitters, such as norepinephrine, epi-nephrine, ACh, serotonin, and dopamine. The concentration in the brain of these bioactive substances appears to be carefully regulated. On the other hand, the biochemical precursors of these transmitters can pass relatively easily, although usually by active transport, from the blood to the brain, and this ensures an adequate supply of locally synthesized transmitters. By and large, the precursors are inactive biologically or have only minimal biological activity. The amino acid transmitters GABA, glycine, glutamic acid, and aspartic acid are actively taken up by the brain capillaries, but ordinarily the transport system for these amino acids is close to saturation. Therefore, a sudden increase in blood concentration of these substances would have little effect on brain levels. Peptide transmitters will not readily penetrate the brain from the circulation, and they are synthesized in the brain.

The blood-brain barrier is not found in all parts of the brain. Certain small areas, including the area postrema beneath the floor of the fourth ventricle, an area in the preoptic recess, and portions of the floor of the third ventricle surrounding the stalk of the pituitary, appear to be devoid of this barrier.

The ability of the blood-brain barrier to exclude entry of a number of drugs into the brain has several therapeutic implications. Many drugs, most notably certain antibiotics, are relatively excluded from the brain. In the treatment of infectious diseases of the CNS, the physician must, in addition to establishing the organism's drug sensitivity, either select an agent that can get to the site of the infection or use a route (intrathecal) that bypasses the barrier. In the human fetus and newborn, the barrier is not as well developed as it is in later life. This fact also must be taken into consideration when one is prescribing drugs during pregnancy and for neonates (see Chapter 6).

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