Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents.

Following experimental traumatic brain injury (TBI), a rapid and significant necrosis occurs at the site of injury which coincides with significant mitochondrial dysfunction. The present study is driven by the hypothesis that TBI-induced glutamate release increases mitochondrial Ca(2+)cycling/overload, ultimately leading to mitochondrial dysfunction. Based on this premise, mitochondrial uncoupling during the acute phases of TBI-induced excitotoxicity should reduce mitochondrial Ca(2+) uptake (cycling) and reactive oxygen species (ROS) production since both are mitochondrial membrane potential dependent.

Proteomic identification of oxidized mitochondrial proteins following experimental traumatic brain injury.

Experimental traumatic brain injury (TBI) results in a significant loss of cortical tissue at the site of injury, and in the ensuing hours and days a secondary injury exacerbates this primary injury, resulting in significant neurological dysfunction. The mechanism of the secondary injury is not well understood, but evidence implicates a critical role for mitochondria in this cascade. This mitochondrial dysfunction is believed to involve excitotoxicity, disruption of Ca(2+) homeostasis, production of reactive oxygen species (ROS), ATP depletion, oxidative damage of mitochondrial proteins, and an overall breakdown of mitochondrial bioenergetics.