INCREASED INTRACELLULAR CA2-ISCHEMIA AND REPERFUSION IN THE RAT - A POSSIBLE CAUSE OF DELAYED NEURONAL DEATH( CONCENTRATION IN THE HIPPOCAMPAL CA1 AREA DURING GLOBAL)

The crucial role of free cytosolic Ca2+ in ischemic neuronal damage ha s been studied in recent years. In the present report, changes in the intracellular Ca2+ concentration in the hippocampal CAI area during tr ansient global ischemia and reperfusion were measured using in vivo Ca 2+ fluorometry with fura-2 in the four-vessel occlusion and reperfusio n model in halothane-anesthetized rats. Marked changes were seen durin g 10-min global ischemia, with the intracellular Ca2+ concentration in creasing gradually following application of the ischemic insult and ra pidly about 2 min after the beginning of ischemia, and continuing to i ncrease until reperfusion. On reperfusion, the intracellular Ca2+ conc entration began to decrease and returned to the pre-ischemic level wit hin 15 min. Induction of severe global ischemia was confirmed by the c omplete suppression of synaptic activity and the decrease in hippocamp al temperature in the CA1 area. After seven days, CA1 pyramidal cell l oss was observed histopathologically in the same rats which had underg one measurement of the intracellular Ca2+ concentration changes. In th e present study, a temporal profile of the free cytosolic Ca2+ dynamic s during ischemic and early post-ischemic period was determined in viv o. The results demonstrate that the intracellular Ca2+ concentration i n the hippocampal CAI area is transiently and markedly increased durin g a brief ischemia-inducing delayed neuronal death, implying that Ca2 overload during cerebral ischemia is a possible cause of the delayed cell death of CAI pyramidal neurons. (C) 1998 IBRO. Published by Elsev ier Science Ltd.