Osmotic opening of the blood-brain barrier

Abstract

The blood-brain barrier at cerebral blood vessels is due to a continuous lining of endothelial cells, which are connected by tight junctions that restrict intercellular diffusion. The endothelium excludes most water-soluble solutes and proteins but supports facilitated stereospecific transport of monosaccharides and large neutral and basic amino acids. The barrier in different species can be made permeable by infusing a hypertonic solution of urea or arabinose into the internal carotid artery. Endothelial cells presumably shrink and tight junctions between them widen to proteins and normally restricted solutes. Thus, intravascular protein tracers such as Evans' blue-albumin, 125I-labelled albumin, horseradish peroxidase (ED 1.11.1.7) and alpha-mannosidase (EC 3.2.1.24) are allowed into the brain, and uptake of [3H] norepinephrine (noradrenaline) is increased more than twofold above a normal rate of accumulation by brain. Osmotic barrier opening to amines has been used to demonstrate their effect on cerebral blood flow from within the brain parenchyma. Osmotic barrier opening is reversible, may be graded with respect to molecular size and is not followed by evidence of brain damage or of brain oedema (when measured two days after hypertonic infusion). Transient cerebral changes probably accompany osmotic opening, however, as glucose uptake and cerebral metabolism of glucose are increased after hypertonic infusion.