Effects of Exposure to Blast Overpressure on Intracranial Pressure and Blood-Brain Barrier Permeability in a Rat Model

<div><p>Exposure to blast overpressure (BOP) activates a cascade of pathological processes including changes in intracranial pressure (ICP) and blood-brain barrier (BBB) permeability resulting in traumatic brain injury (TBI). In this study the effect of single and multiple exposures at two intensities of BOP on changes in ICP and BBB permeability in Sprague-Dawley rats was evaluated. Animals were exposed to a single or three repetitive (separated by 0.5 h) BOPs at 72 kPa or 110 kPa. ICP was monitored continuously via telemetry for 6 days after exposure to BOP. The alteration in the permeability of BBB was determined by extravasation of Evans Blue (EB) into brain parenchyma. A significant increase in ICP was observed in all groups except the single 72 kPa BOP group. At the same time a marked increase in BBB permeability was also seen in various parts of the brain. The extent of ICP increase as well as BBB permeability change was dependent on intensity and frequency of blast.</p></div

Representative images of EB fluorescence in brains of sham-controls and rats exposed to single or repetitive BOP at two different intensities (72 kPa vs 110 kPa).

<p>Sections of brain were analyzed for EB fluorescence in frontal cortex (FCX), hippocampus (HIP), thalamus (THL), and occipital cortex (OCX). The EB fluorescence was increased after exposure to BOP suggesting higher vascular leakage into brain parenchyma.</p

Time course of changes in ICP in response to exposure to BOP.

<p>For each day (marked with vertical dashed lines) a three or four hour segment of data is presented. A) 1x72 kPa; B)3x72 kPa; C) 1x110 kPa; and D) 3x110 kPa. Data are expressed as means ± SE (n = 6 in each group). b—time of blast; * p<0.01—significance of differences in ICP between two adjacent time points, # p<0.01—significance of differences in ICP compared to pre-blast baseline.</p

Quantification of EB fluorescence intensity in sham and blast exposed rats.

<p>Results are shown as relative EB fluorescence units (controls = 1) and are expressed as means ± SE (n = 6). A) Comparison between groups 1x72 kPa and 3x72 kPa; B) 1x110 kPa and 3x110 kPa; C) 1x72 kPa and 1x110 kPa; D) 3x72 kPa and 3x110 kPa. *p<0.05—difference between sham and BOP exposed groups. #p<0.05—difference between BOP exposed groups. FCX: frontal cortex; HIP: hippocampus; THL: thalamus; OCX: occipital cortex.</p