Tight-junctional modification as the basis of osmotic opening of the blood-brain barrier

Abstract

Osmotic opening of the blood-brain barrier (BBB) most likely is mediated by modification of interendothelial tight junctions, subsequent to shrinkage of cerebrovascular endothelial cells, and not by stimulation of transendothelial vesicular transport or by channel formation. This paper summarizes evidence for this conclusion: osmotic BBB opening is mediated by endothelial cell shrinkage, electron microscopy, with single or serial thin sections, demonstrates penetration of intravascular tracer into brain via tight junctional complexes, the BBB remains open after the brain is fixed, osmotic BBB opening is rapidly reversible, and is insensitive to phenothiazines, and BBB closure following osmotic treatment is size-dependent, indicative of a sieve (pore) mechanism with bulk flow. The entire mechanism of vesicular transport in normal tissue is, furthermore, in doubt, because vesicles that are found in tissue layers connected by tight junctions (e.g., frog nerve perineurium and capillary endoneurium) do not support macromolecular transport.