Heterogeneous regional and temporal energetic impairment following controlled cortical impact injury in rats

Objectives: Following traumatic brain injury metabolic stability is impaired. Duration and reversibility of these changes might be important to guide specific interventions. Methods: To characterize temporal and regional changes in cerebral metabolism, 68 male Sprague-Dawley rats were subjected to a focal cortical contusion. Lesion progression and mitochondrial impairment were determined by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride (TTC) staining, respectively. Metabolic alterations were determined at hours 6 and 24 and day 7 by measuring extracellular glucose, lactate and hypoxanthine levels with microdialysis catheters placed adjacent and distant to the contusion and by quantifying changes in tissue ATP, lactate and glucose using bioluminescence imaging. Results: The cortical lesion reached its maximal extent at hour 24 and remained confined to the ipsilateral hemisphere. In microdialysate, at hour 6, extracellular hypoxanthine and lactate reached maximal values, thereafter hypoxanthine normalized while lactate remained increased. Extracellular glucose reached the highest values at hour 24 and remained elevated. Bioluminescence imaging revealed heterogeneous changes in areas distant to the contusion. No significant changes were found in ATP content. Slightly elevated tissue glucose until 24 hours in the ipsilateral hemisphere was observed. Following a continuous increase, lactate levels were the highest by 6 hours in the ipsilateral cortex and hippocampus. Discussion: CCI is associated with disturbances in energetic metabolism. Metabolic perturbation is not restricted to the early phase and the contusional region following focal cortical contusion, but also involves hippocampus and primarily uninjured parts of the hemisphere.