Role of extracellular proteins in the dynamics of vasogenic brain edema

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Abstract
The relationship between extravasation of protein into extracellular spaces of brain parenchyma and the water content of such regions were evaluated in an experimental model. In this model, a temporary opening of the blood-brain barrier (BBB) to proteins was produced without significant injury to the cellular elements of brain tissue. Rabbits were subjected to bolus injection of their own blood under 360–400 mm Hg pressure via the internal carotid artery. The opening of the barrier and its duration were evaluated with Evans blue (EB), horseradish peroxidase (HRP), and sodium fluorescein (NaFl) tracers. The water content of brain tissue was assessed by specific gravity (SG) measurements in 1-mm-diameter tissue samples. Quantitative evaluation of protein penetration into brain tissue was carried out using125I bovine serum albumin (BSA). The opening of the BBB to proteins persisted up to 9 h, whereas the barrier remained permeable to small molecular NaFl for 24 h. The SG measurements indicated in the areas of EB extravasation a progressive increment in water content up to 9 h, i.e., the duration of BBB opening to proteins. Following this, there was a progressive clearance of edema in spite of the BBB remaining open for NaFl for 24 h. Quantitative evaluations of125I-BSA and SG in the same tissue samples, supported by statistical analysis, indicated approximately linear relationship between albumin and water, implying a strong correlation between the development of vasogenic edema and extravasation of proteins into extracellular spaces.