Extravasation, spread and cellular uptake of Evans blue-labelled albumin around a reproducible small stab-wound in the rat brain.

A small stab wound was made in the frontal lobe of the rat brain in order to study both the acute damage and the restitution of the blood-brain barrier to macromolecules under well-defined experimental conditions. Intravenously administered Evans blue-labelled albumin (EBA) was used as a tracer and the brain sections were observed in a fluorescence microscope. EBA leaked into the neuropil only during the first 3 days after the trauma. The maximal leakage occurred during the first day after the injury. The tracer spread from the area surrounding the stab wound in a reproducible way, initially roughly centrifugally. Nerve and glial cells close to the wound displayed a diffuse fluorescence of their cell bodies 1 to 6 h after the injury, i.e. at times with maximal extravasation of the tracer. A more granular distribution of the tracer was seen in neurons and glial cells at both very short and long times after EBA injection. Thus, the blood-brain barrier lesion induced was reproducible and reversible as judged by the pattern of EBA leakage. Some cells immediately adjacent to the injury had a diffuse cytoplasmic distribution of the tracer complex, in contrast to cells more distant from the injury, having a more granular distribution of the tracer in their cytoplasm. However, the appearance of the fluorescence in neurons and glia was to a large extent dependent upon the time after the injury, at which the cells were exposed to the tracer complex and on the time that had elapsed from the time of injection of the tracer complex to the sacrifice of the animal. Thus, it seems likely that two factors contribute to the appearance of the neuronal EBA distribution: on one hand the location and possibly extent of cellular damage of the cell, and, on the other hand, the time and amount of EBA to which the cells were exposed.