Early mitochondrial dysfunction after cortical contusion injury.
Following traumatic brain injury, mitochondria sustain structural and functional impairment, which contributes to secondary damage that can continue for days after the initial injury. The present study investigated mitochondrial bioenergetic changes in the rat neocortex at 1 and 3 h after mild, moderate, and severe injuries. Brains from young adult Sprague-Dawley rats were harvested from the injured and contralateral cortex to assess possible changes in mitochondrial respiration abilities following a unilateral cortical contusion injury. Differential centrifugation was used to isolate synaptic and extrasynaptic mitochondria from cortical tissue. Bioenergetics was assessed using a Clark-type electrode and results were graphed as a function of injury severity and time post-injury. Respiration was significantly affected by all injury severity levels compared to uninjured tissue. Complex 1- and complex 2-driven respirations were affected proportionally to the severity of the injury, indicating that damage to mitochondria may occur on a gradient. Total oxygen utilization, respiratory control ratio, ATP production, and maximal respiration capabilities were all significantly decreased in the injured cortex at both 1 and 3 h post-trauma. Although mitochondria displayed bioenergetic deficits at 1 h following injury, damage was not exacerbated by 3 h. This study stresses the importance of early therapeutic intervention and suggests a window of approximately 1-3 h before greater dysfunction occurs.
Gilmer
Lesley K
LK
Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.
Roberts
Kelly N
KN
Joy
Kelly
K
Sullivan
Patrick G
PG
Scheff
Stephen W
SW
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley