Changes of cerebral energy metabolism and lipid peroxidation in rats leading to mitochondrial dysfunction after diffuse brain injury

The effect of mild closed head trauma, induced by the weight-drop method (4 50 g from a l-m height), on lipid peroxidation and energy metabolism of bra in tissue was determined at various times after cerebral injury in spontane ously breathing rats (1, 10, 30 minutes and 2, 6, 15, 24, 48, and 120 hours ). Animals were continuously monitored for the evaluation of blood pressure , blood gases, heart rate, and intracranial pressure. Analysis of malondial dehyde (MDA) as an index of lipid peroxidation, ascorbic acid, high-energy phosphates, nicotinic coenzymes, oxypurines, and nucleosides was performed by high-performance liquid chromatography (HPLC) on neutralized perchloric acid extract of the whole brain. Data showed that MDA, undetectable in cont rol, sham-operated rats, was already present within 1 minute of trauma (1.7 7 nmol/g wet weight; SD = 0.29) and reached maximal values by 2 hours (72.2 6 nmol/l w.w.; SD = 11.26), showing a progressive slow decrease thereafter. In contrast, ATP, GTP, and nicotinic coenzyme (NAD and NADP) concentration s showed significant reduction only by the second hour postinjury. Maximal decrease of the ATP and GTP concentrations were sceen at 6 hours postinjury , whereas NAD and NADP concentrations showed maximum decline by 15 hours. V alues recorded in mechanically ventilated rats did not differ significantly from those obtained in spontaneously breathing animals. These findings, su pported by the absence of blood gas and blood pressure changes in the spont aneously breathing rats, strongly support the premise that biochemical chan ges (primarily lipid peroxidation) are not caused by secondary ischemic-hyp oxic phenomena but rather are triggered by these forces acting on the brain at the time of impact. In addition, these results suggest that depression of energy metabolism might be caused by peroxidation of the mitochondrial m embrane with a consequent alteration of the main mitochondrial function-tha t is, the energy supply.