Cerebral metabolic state following complete compression ischemia

Recovery of cerebral metabolism after total ischemia was studied in rats by measurements of brain tissue concentrations of carbohydrate substrates, amino acids and organic phosphates at various periods (1–180 min) following an increase in the intracranial CSF pressure to values exceeding the mean arterial blood pressure. Control experiments were performed to evaluate the recovery of the EEG and of gross neurological function. Following ischemia of up to 15 min duration there was rapid rephosphorylation of PCr and ATP suggesting that mitochondrial function was adequately resumed. Furthermore, since the AMP levels were completely normalized and since accumulated lactate disappeared the data exclude the possibility that any significant proportion of the tissue remained unperfused. After periods of ischemia lasting 5 min or more EEG or gross neurological function did not normalize within the period studied (180 min). Although the adenylate energy charge returned to normal after 3 min of ischemia significantly subnormal values were obtained after 7.5 and 15 min of ischemia, suggesting that a biochemical lesion may have occurred. Recirculation of the tissue after ischemia was followed by disappearance of accumulated ammonia and by replenishment of citric cycle intermediates. However, α-ketoglutarate and malate showed slightly subnormal values after 180 min. Furthermore, there was a permanent decrease in glutamate and a late increase in glutamine indicating a lingering derangement in the amino acid metabolism that many have functional implications.