Ultrastructural studies on cerebrovascular permeability in acute hypertension

Acute hypertension, experimentally induced by intravenous injection of metaraminol in adult rabbits, rapidly induced a damage of the blood-brain barrier in the cerebral cortex, as visualized by Evans-blue-conjugated albumin and horseradish peroxidase. Extravasation of these two exogenous tracers was demonstrated to occur in arterioles, in capillaries and, rarely, in venules. Peroxidase passed the endothelial cell into the nervous tissue in either or three different ways, i.e. through channels, often sigmoidshaped, in the cytoplasm, and transendothelial pinocytosis. The third pathway could, although rarely, be demonstrated between adjacent endothelial cells after cleavage of junctional complexes. The tracer peroxidase was further spread along the blood vessel within the basement membrane and in the extracellular space of the brain. Damaged endothelial cells with diffuse cytoplasmic peroxidase activity and large vesicles were occasionally observed within the areas with blood-brain barrier injury. There were also signs of increased pinocytotic activity in endothelial cells outside the barrier damaged cortical areas. Nerve cells and neuroglial cells could show either a diffuse cytoplasmic peroxidase activity or a vesicular location of the tracer, or sometimes both. The observations are discussed in relation to previous studies on the mechanism of transendothelial passage of protein tracers at blood-brain barrier damage.