Effect of Hypothermia on ATP and Hydroxyl Radical Levels in Hippocampus during Cerebral Ischemia/Reperfusion

OBJECTIVE To study the effect of hypothermia on ATP and hydroxyl radical levels in hippocampus during cerebral ischemia/reperfusion,and investigate the relationship between the change of their content and delayed neuronal death.METHODS Forebrain ischemia in gerbils was produced by occlusion of bilateral common carotid arteries using aneurysm clamps,and the insult time was 10 min.Gerbils were randomly divided into sham-operated group,normothermia group and hypothermia group.Both normothermia group and hypothermia group were further divided into 3 subgroups according to the reperfusion time(6 h,48 h and 96 h).The brain temperature in all gerbils during cerebral ischemia was kept at 38±0.2℃,and it was kept at 30±0.2℃ within 6 h of reperfusion in hypothermia group.However,the brain temperature in normothermia group was kept at 38±0.2℃.The number of surviving neurons in hippocmpal CA1 sector in 100 μm2 was counted(n=5).ATP,ADP,AMP and hydroxyl radical levels were determined by high liquid chromatography(n=8).RESULTS The number of surviving neurons in hippocampal CA1 sector after reperfusion 96 h in normothermia group was only 5±2/100 μm2,much less than that in sham-operated group(96±12/100 μm2)(P0.01).The number of surviving neurons in hippocampal CA1 sector after reperfusion 96 h in hypothermia group was 45±13/100 μm2,much more than that in normothermia group(P0.01).ATP and adenine nucleotide pool levels in hippocampus in normothermia group significantly decreased after reperfusion(P0.01).ATP and adenine nucleotide pool levels in hippocampus in hypothermia group were much more than that in normothermia group after reperfusion 48 h and 96 h(P0.05).The 2,3-DHBA outputs after reperfusion 6 h in normothermia group increased by 132% of that in sham-operated group(P0.01),but there was no significant difference of 2,3-DHBA outputs between normothermia group and sham-operated group after reperfusion 48 h and 96 h.There was also no significant difference of 2,3-TDHBA outputs between hypothermia group and sham-operated group.The 2,3-DHBA outputs after reperfusion 6 h in hypothermia group was much lower than that in normothermia group(P0.05).CONCLUSION The persist failure of energy metabolism could lead to the delayed neuronal death after cerebral ischemia.Hypothermia could prevent delayed neuronal death by attenuating the persist failure of energy metabolism.