POOR RECOVERY OF MITOCHONDRIAL REDOX STATE IN CA1 AFTER TRANSIENT FOREBRAIN ISCHEMIA IN GERBILS

Background and Purpose-Several investigations have detected evidence o f apoptosis in delayed neuronal death, but controversy prevails regard ing this point. Recent studies have implicated mitochondria in apoptot ic events. To explore relationships between delayed neuronal death and dysfunction of the respiratory chain, we analyzed mitochondrial redox changes in the gerbil hippocampus. Methods-We assessed the mitochondr ial redox state in gerbil hippocampus before, during, and at various t ime points after 5 minutes of forebrain ischemia. The redox state was examined with a low-temperature fluorometer. Fluorescence signals of f lavoprotein and NADH were measured, and their fluorescence ratio was c alculated as a mitochondrial redox ratio (MRR) equal to flavoprotein/( flavoprotein+NADH). Results-Ischemia increased NADH and decreased flav oprotein signals in all hippocampal areas, but reduction in MRR was gr eater in CAI than in other areas of the hippocampus. immediately after recirculation, MRR recovery was delayed in the CAI and the dentate gy rus, and the reduction in MRR persisted in CA1. Conclusions-These resu lts suggest that during ischemia CAI experiences more pronounced hypox ia (state V) than less vulnerable regions. Persistent MRR reduction in CAI is attributed to dysfunction of the electron transport system, an d this phenomenon may be importantly involved in apoptosis.