Mitochondrial dysfunction early after traumatic brain injury in immature rats.
Mitochondria play central roles in acute brain injury; however, little is known about mitochondrial function following traumatic brain injury (TBI) to the immature brain. We hypothesized that TBI would cause mitochondrial dysfunction early (<4 h) after injury. Immature rats underwent controlled cortical impact (CCI) or sham injury to the left cortex, and mitochondria were isolated from both hemispheres at 1 and 4 h after TBI. Rates of phosphorylating (State 3) and resting (State 4) respiration were measured with and without bovine serum albumin. The respiratory control ratio was calculated (State 3/State 4). Rates of mitochondrial H(2)O(2) production, pyruvate dehydrogenase complex enzyme activity, and cytochrome c content were measured. Mitochondrial State 4 rates (ipsilateral/contralateral ratios) were higher after TBI at 1 h, which was reversed with bovine serum albumin. Four hours after TBI, pyruvate dehydrogenase complex activity and cytochrome c content (ipsilateral/contralateral ratios) were lower in TBI mitochondria. These data demonstrate abnormal mitochondrial function early (<or=4 h) after TBI in the developing brain. Future studies directed at reversing mitochondrial abnormalities could guide neuroprotective interventions after pediatric TBI.
Robertson
Courtney L
CL
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA. croberts@peds.umaryland.edu
Saraswati
Manda
M
Fiskum
Gary
G
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000473:pathology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology / Q000648:ultrastructure; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure; D007658:Ketone Oxidoreductases / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000473:pathology / Q000502:physiology*; D010101:Oxygen Consumption; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D017382:Reactive Oxygen Species; D045304:Cytochromes c; D007658:Ketone Oxidoreductases; C053164:pyruvate dehydrogenase (NADP+); D010751:Phosphopyruvate Hydratase