Blood Brain Barrier Permeability and Acute Inflammation in Two Models of Traumatic Brain Injury in the Immature Rat: A Preliminary Report

Abstract

We sought to investigate the course and magnitude of blood brain barrier (BBB) permeability following focal and diffuse traumatic brain injury (TBI) in immature rats and examine the time course of markers of acute inflammation (neutrophil accumulation and E-selectin [E-sel] expression) following these two types of injury. We measured BBB permeability using IV injection Evans Blue (EB) and the extent of inflammation using immunohistochemical techniques identifiying neutrophils (monoclonal antibody RP-3) and the endothelial adhesion molecule, E- selectin. Male Sprague-Dawley immature (17 day-old) rats (30-45g, n=80) were subjected to a controlled cortical impact (CCI: 2mm, 4m/s), a closed head diffuse injury (DI: 150g/2m) or a corresponding sham procedure (with or without craniotomy). EB was injected IV at 30min before sacrifice, which occurred at 1h, 4h, or 24h after injury. BBB permeability was observed in both the CCI and DI rats at 1h after injury which largely resolved by 24h. In the CCI, EB extravasation was seen within and around the contusion. In DI, diffuse BBB permeability was seen, DI was not associated with acute inflammation since there was neither neutrophil accumulation nor E-selectin expression. The CCI rats though had 5.1 ± 2.2 neutrophils/ hpf and 3.0 ± 0.4 endothelial cells/hpf expressing E- selectin (mean ± SEM) (both p < 0.05 vs sham and DI). These data suggest that BBB breakdown occurs in the immature rat after both focal and diffuse TBI. This early BBB permeability was not associated with acute inflammation in DI but was in CCI. These data also suggest that contusion is a key factor in the development of a tradtional acute inflammatory response after TBI in the immature rat.