The Effects of Blast-Induced Neurotrauma on Blood-Brain Barrier Permeability, Cell-Cell Junction Protein Levels and the Role of Peroxynitrite


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Traumatic brain injury is one of the most common injuries presented in emergency departments in the U.S.. While mild traumatic brain injury (TBI) is often not reported or treated it may still result in significant pathophysiological disruptions for the patient. As a result of the ongoing military Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF), service men and women are returning home after deployment with mild TBI (mTBI). This has resulted in mild TBI becoming the signature injury of these operations and has presented a substantial challenge for researchers and clinicians alike. Blast-induced Neurotrauma (BINT), often caused by improvised explosive devices (IEDs), is an injury that affects military personnel, however, the increasing threat of worldwide terrorist attacks makes this a concern for all individuals. Many of those who are subjected to blast overpressures and underpressures experience deficits in cognition, memory, sleep, behavior and mood. Because the effects of blast exposure are not well defined on a cellular level, there is still a need for effective interventions and therapeutics. Here we will discuss a novel rodent model for the study of blast-induced neurotrauma, which we used to investigate the effects of BINT on the blood-brain barrier, cognitive and sensorimotor function and reactive nitrogen species formation. We hypothesize that BINT increases the permeability of the BBB, decreases the presence of the tight junction protein, occludin, in cerebral blood vessels, causes deficits in sensorimotor function and spatial learning and working-memory, and increases the formation of potent oxidant, peroxynitrite. A better understanding of the direct and indirect effects of blast exposure on the brain will contribute to our understanding of the mechanisms responsible for the unique pathology associated with BINT.



traumatic brain injury, blast injury, blood-brain barrier, neurotrauma