Blood-brain barrier permeability in an experimental model of bacterial cerebritis

Abstract

The mechanisms affecting blood-brain barrier (BBB) permeability in a brain abscess are not well defined. We sought to determine whether one bacterial species, Staphylococcus aureus, when inoculated into the brain, can cause the BBB to become abnormally permeable before leukocytes begin migrating into the brain. Cerebritis was induced by inoculating a suspension of S. aureus into the brain of the rat. The extent of leukocyte migration into the brain was assessed from histological sections at sequential times after the injection. BBB permeability was assessed by 1) detecting the presence of serum albumin leakage into the brain with a fluorescein-labeled antibody to rat albumin, and 2) detecting evidence of staining of the brain parenchyma with Evans blue dye. The fluorescein labelled anti-rat albumin antibody studies showed that the BBB was immediately damaged in experimental and control animals by the process of inoculation, but remained open to a greater extent in subjects inoculated with bacteria. Within 6 hours after inoculation, neutrophils began migrating into bacteria-inoculated brains. Evans blue dye, however, did not become detectable in the surrounding parenchyma until 72 hours later, long after leukocyte migration had occurred. The findings indicate that an acute disruption of the BBB in the needle track precedes leukocyte influx, but a more widespread increase in regional BBB permeability does not occur until 3 days after the bacterial inoculation. The time course for the development of increased vascular permeability suggests that a delayed product of the inoculation caused impairment of the regional BBB.