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 following reperfusion. A characteristic event during reoxygenation after anoxia in hippocampal slices is hyperoxidation of the electron carriers of the mitochondrial respiratory chain. Earlier studies suggested that calcium influx due to loss of ion homeostasis during anoxia was linked to neuronal damage. Since a link between cytosolic calcium overload and post-anoxic hyperoxidation (PAMHo) has been suggested in previous studies, present studies sought to test the hypothesis that the length of anoxic depolarization can influence hyperoxidation and electrical activity recovery following anoxia in hippocampal slices. Rat hippocampal 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 scanning 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 here that mitochondrial hyperoxidation and synaptic activity in hippocampal slices are highly sensitive to the time in which slices remain depolarized (AD). Copyright 1998 Elsevier Science B.V.