Testing of a hypothesis for osmotic opening of the blood-brain barrier.

RAPOPORT, STANLEY I., MASAHARU, HORI, AND IGOR KLATZO. Testing of a hypothesis for osmotic opening of the blood-brain barrier. Am. J. Physiol. 223(Z) : 323-331. 1972.-It is hypothesized that some concentrated solutions open the blood-brain barrier to the Evans lllue-albumin complex by shrinking barrier cells and opening up the spaces between them. Four experimental criteria are required if the action of these solutions is consistent with this hypothesis. The solute should act reversibly, it should not act on the barrier lIecause of a specific drug action, its damaging effect should increase with increasing concentration, and its effect should be related inversely to its ability to penetrate the cell membrane. Concentrated solutions of electrolytes and nonelectrolytes were applied to the pia-arachnoid surface of the rabbit cerebral cortex to study opening of the barrier of the pia-arachnoid blood vessels to the intravascular Evans blue-albumin complex. The electrolutes and relatively lipid insoluble nonelectrolytes opened up the iiarrier reversibly and acted consistently with the four criteria of the osmotic hypothesis. The more lipid soluble nonelectrolytes ciamaged the barrier irreversibly and would not be expected to act osmotically. Intracarotid perfusion of solutions of concentrated urea, which is relatively lipid insoluble, opened up the Mood-brain barrier at the brain capillaries reversibly, while solutions of the more lipid soluble propylene glycol opened it irreversibly, consistent with topical observations. The bloodbrain barrier acts like a layer of cells, probably the endothelial cells of the cerebral vascular system.