Acute mitochondrial dysfunction after blast exposure: potential role of mitochondrial glutamate oxaloacetate transaminase.

Use of improvised explosive devices has significantly increased the incidence of traumatic brain injury (TBI) and associated neuropsychiatric deficits in the recent wars in Iraq and Afghanistan. Acute deleterious effects of single and repeated blast exposure can lead to long-term neurobiological effects and neuropsychiatric deficits. Using in vitro and in vivo shock tube models of blast-induced TBI, we studied changes in mitochondrial energy metabolism after blast exposure. Single and repeated blast exposures in vitro resulted in significant decreases in neuronal adenosine triphosphate (ATP) levels at 6 h post-blast that returned towards normal levels by 24 h. Similar changes in ATP also were observed in the cerebral cortices of mice subjected to single and repeated blast exposures. In neurons, mitochondrial glutamate oxaloacetate transaminase (GOT2) plays a critical role in metabolism and energy production. Proteomic analysis of brain cortices showed a significant decrease in GOT2 levels 6 h after repeated blast exposures, which was further confirmed by Western blotting. Western blot analysis of GOT2 and pyruvate dehydrogenase in the cortex showed direct correlation only between GOT2 and ATP levels. Activity of GOT2 in the isolated cortical mitochondria also showed significant decrease at 6 h supporting the results of proteomic and Western blot analyses. Knowing the significant role of GOT2 in the neuronal mitochondrial energy metabolism, it is quite likely that the down regulation of GOT2 after blast exposure is playing a significant role in mitochondrial dysfunction after blast exposure.