Free radical biology & medicine
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Free Radic. Biol. Med. · Jul 2013
Induction of oxidative and nitrosative damage leads to cerebrovascular inflammation in an animal model of mild traumatic brain injury induced by primary blast.
We investigate the hypothesis that oxidative damage of the cerebral vascular barrier interface (the blood-brain barrier, BBB) causes the development of mild traumatic brain injury (TBI) during a primary blast-wave spectrum. The underlying biochemical and cellular mechanisms of this vascular layer-structure injury are examined in a novel animal model of shock tube. We first established that low-frequency (123kPa) single or repeated shock wave causes BBB/brain injury through biochemical activation by an acute mechanical force that occurs 6-24h after the exposure. ⋯ The detection of brain cell proteins neuron-specific enolase and S100β in the blood samples validated the neuroastroglial injury in shock-wave TBI. Our hypothesis that cerebral vascular injury occurs before the development of neurological disorders in mild TBI was further confirmed by the activation of caspase-3 and cell apoptosis mostly around the perivascular region. Thus, induction of oxidative stress and activation of matrix metalloproteinases by shock wave underlie the mechanisms of cerebral vascular BBB leakage and neuroinflammation.