Electrophysiological Correlates of Peroxide Damage in Guinea Pig Hippocampus In Vitro

摘要

Active oxygen (superoxide, peroxide and hydroxyl radicals) and other free radicals occur naturally as intermediates in oxidative metabolism. There are many enzymes and free radical scavengers present in normal tissue to maintain these compounds within non-toxic levels. In some pathological states of the nervous system, however, free radicals in brain tissue can increase to abnormally high levels. One such state is ischemia and subsequent reperfusion. The free radicals produced by this insult are likely to react with unsaturated fatty acids and initiate lipid peroxidation, disrupting the integrity of cell membranes. CA1 neurons of the hippocampus are particularly sensitive to ischemic damage. The present study was initiated to determine the electrophysiological correlates of active oxygen damage in CA1 pyramidal cells of the hippocampus in vitro. Hydrogen peroxide was combined with ferrous sulfate to generate hydroxyl free radicals. Through analysis of the dendritic and somatic field potentials, it was found that synaptic efficacy and spike generation mechanisms were impaired. Male guinea pigs were killed by cervical dislocation under halothane anesthesia. The brain was removed and immediately placed in oxygenated, iced solution (composition below). Within 5 min both hippocampi were dissected and thin slices were cut.