PROLONGED ANOXIC DEPOLARIZATION EXACERBATES NADH HYPEROXIDATION AND PROMOTES POOR ELECTRICAL RECOVERY AFTER ANOXIA IN HIPPOCAMPAL SLICES

Mitochondrial dysfunction appears to occur during brain ischemia and f ollowing reperfusion. A characteristic event during reoxygenation afte r anoxia in hippocampal slices is hyperoxidation of the electron carri ers of the mitochondrial respiratory chain. Earlier studies suggested that calcium influx due to loss of ion homeostasis during anoxia was l inked to neuronal damage. Since a link between cytosolic calcium overl oad and post-anoxic hyperoxidation (PAMHo) has been suggested in previ ous studies, present studies sought to test the hypothesis that the le ngth of anoxic depolarization can influence hyperoxidation and electri cal activity recovery following anoxia in hippocampal slices. Rat hipp ocampal slices were made anoxic and then allowed to recover for 60 min . The time of anoxia was defined by the time of anoxic depolarization (AD), and slices were divided in five groups: 0.5, 1, 2, 5 and 10 min of AD. Reduction/oxidation shifts of NADH were measured by rapid scann ing spectrofluorometry. Synaptic activity was indicated by population spike amplitudes in the CA1 pyramidal cell subfield of the hippocampus in response to stimulation of the Schaffer collaterals. We report her e that mitochondrial hyperoxidation and synaptic activity in hippocamp al slices are highly sensitive to the time in which slices remain depo larized (AD). (C) 1998 Elsevier Science B.V.