Regional metabolite profiles in early stages of global ischemia in the gerbil.

The present experiments were designed to determine the short-term regional changes in the cyclic nucleotides, certain glucose metabolites, high-energy phosphates, gamma-aminobutyric acid (GABA), glutamate, and glutamine in the gerbil brain following bilateral ligation of the common carotid arteries. The brains of the animals were microwaved at 20, 40, 60, 90, 120, and 300 sec of ischemia and the metabolites were measured in the cerebral cortex, hippocampus, and striatum. There were significant decreases in ATP, P-creatine, and glucose within the first 20 sec of ischemia in all three regions examined, whereas the increases in phosphate and lactate, as well as the loss of glycogen, were evident only after 40 sec of ischemia. The high-energy phosphates were essentially depleted (less than 15% of control values) in all three regions by 2 min of ischemia, indicating that the energy imbalance elicited by ischemia was comparable in the three regions. In contrast, the magnitude of the changes in the cyclic nucleotides was greater in the hippocampus than in the cerebral cortex or striatum. In addition, the decrease in cyclic GMP levels at 20 sec of ischemia preceded the increases in cyclic AMP observed at 40 sec in all three regions. The use of microwave irradiation to fix the gerbil brains not only provides a more accurate assessment of the time course of the metabolite changes but also permits studies on the deeper regions of the brain than is possible with freezing techniques.