Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury.
Traumatic brain injury (TBI) is associated with primary and secondary injury. A thorough understanding of secondary injury will help to develop effective treatments and improve patient outcome. In this study, the GM model of controlled cortical impact injury (CCII) of Lighthall (1988) was used with modification to induce lateral TBI in rats. Forebrain mitochondria isolated from ipsilateral (IH) and contralateral (CH) hemispheres to impact showed a distinct difference. With glutamate + malate as substrates, mitochondria from the IH showed a significant decrease in State 3 respiratory rates, respiratory control indices (RCI), and P/O ratios. This decrease occurred as early as 1 h and persisted for at least 14 days following TBI. The State 3 respiratory rates, RCI, and P/O ratios could be restored to sham values by the addition of EGTA to the assay mixture. A significant amount of Ca2+ was found to be adsorbed to the mitochondria of both the IH and the CH with higher values seen in the IH. The rate of energy-linked Ca2+ transport in the IH was significantly decreased at 6 and 12 h. These data indicate that CCII-induced TBI perturbs cellular Ca2+ homeostasis and results in excessive Ca2+ adsorption to the mitochondrial membrane, which subsequently inhibits the respiratory chain-linked electron transfer and energy transduction.
Xiong
Y
Y
Department of Biochemistry, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
Gu
Q
Q
Peterson
P L
PL
Muizelaar
J P
JP
Lee
C P
CP
D000818:Animals; D001921:Brain / Q000648:ultrastructure; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004579:Electron Transport / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D010085:Oxidative Phosphorylation; D016548:Prosencephalon / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D002614:Chelating Agents; D004533:Egtazic Acid; D002118:Calcium