Increase in Blood-Brain Barrier Perrmeability, Oxidative Stress, and Activated Microglia in a Rat Model of Blast-Induced Traumatic Brain Injury

摘要

Traumatic brain injury (TBI) as a consequence of exposure to blast is increasingly prevalent in military populations, with the underlying pathophysiological mechanisms mostly unknown. In the present study, we utilized an air-driven shock tube to investigate the effects of blast exposure (120 kPa) on rat brains. Immediately following exposure to blast, neurological function was reduced. 888 permeability was measured using lgG antibody and evaluating its immunoreactivity in the brain. At 3 and 24 hr postexposure, there was a transient significant increase in lgG staining in the cortex. At 3 days postexposure, lgG immunoreactivity returned to control levels. Quantitative immunostaining was employed to determine the temporal course of brain oxidative stress following exposure to blast. Levels of 4-hydroxynonenal (4-HNE) and 3- nitrotyrosine (3-NT) were significantly increased at 3 hr postexposure and returned to control levels at 24 hr postexposure. The response of microglia to blast exposure was determined by autoradiographic localization of 3H-PK11195 binding. At 5 days postexposure, increased binding was observed in the contralateral and ipsilateral dentate gyrus. These regions also displayed increased binding at 1 0 days postexposure; in addition to these regions there was increased binding in the contralateral ventral hippocampus and substantia nigra at this time point. By using antibodies against CD11 b/c, microglia morphology characteristic of activated microglia was observed in the hippocampus and substantia nigra of animals exposed to blast. These results indicate that BBB breakdown, oxidative stress, and microglia activation likely play a role in the neuropathology associated with TBI as a result of blast exposure.