Increased intracellular Ca2+ concentration in the hippocampal CA1 area during global ischemia and reperfusion in the rat: a possible cause of delayed neuronal death.

The crucial role of free cytosolic Ca2+ in ischemic neuronal damage has been studied in recent years. In the present report, changes in the intracellular Ca2+ concentration in the hippocampal CA1 area during transient global ischemia and reperfusion were measured using in vivo Ca2+ fluorometry with fura-2 in the four-vessel occlusion and reperfusion model in halothane-anesthetized rats. Marked changes were seen during 10-min global ischemia, with the intracellular Ca2+ concentration increasing gradually following application of the ischemic insult and rapidly about 2 min after the beginning of ischemia, and continuing to increase until reperfusion. On reperfusion, the intracellular Ca2+ concentration began to decrease and returned to the pre-ischemic level within 15 min. Induction of severe global ischemia was confirmed by the complete suppression of synaptic activity and the decrease in hippocampal temperature in the CA1 area. After seven days, CA1 pyramidal cell loss was observed histopathologically in the same rats which had undergone measurement of the intracellular Ca2+ concentration changes. In the present study, a temporal profile of the free cytosolic Ca2+ dynamics during ischemic and early post-ischemic period was determined in vivo. The results demonstrate that the intracellular Ca2+ concentration in the hippocampal CA1 area is transiently and markedly increased during a brief ischemia-inducing delayed neuronal death, implying that Ca2+ overload during cerebral ischemia is a possible cause of the delayed cell death of CA1 pyramidal neurons.