Ischemic tolerance phenomenon from an approach of energy metabolism

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The effect of 5 min lethal ischemia on cerebral metabolism and a mitochondrial enzyme, pyruvate dehydrogenase (PDH) activity in the animals treated with or without 2 min sublethal ischemia was studied using mongolian gerbils. Protein synthesis was also studied.The animals with or without pretreatment were induced 5 min lethal ischemia and allowed reperfusion for designated periods. The pretreated animals were given 2 min ischemia 24 hr prior to 5 min ischemic insult.Brain metabolites of ATP,PCr and lactate and PDH activity were determined in the cortex and hippocampus mainly including CA_1 region. Protein synthesis was determined by autoradiography method ; after injecting [^<14>C]-leucine the uptake was measured in CA_1, CA_3', dentate and cortex in the both groups.In 10 min reperfusion lactate levels in the non-pretreated group were lower than those of the pretreated group in cortex, otherwise, there was no difference in metabolism between the pretreated and the non-pretread animals … More in the both areas by reperfusion 3 days. However, the elevation of PDH activity in the hippocampus in the pretreated animals was suppressed in 5 min ischemia. In reperfusion 7 days, marked decrease of ATP and PCr concentrations in hippocampus in the non-pretreated animals, which reflects delayd neuronal death, was noticed, while that in cortex was not noticed.Protein synthesis in the all areas measured markedly decreased compared to each sham controls 1 hr after ischemia. After 1 day, in CA_1 region, protein synthesis in the pretreated animals recovered to 50% of the control, while that in the non-pretreated was about 20% of the control. In other areas protein synthesis quickly recovered to more than 60% of the control in the both groups.In conclusion, the pretreatment of sublethal ischmia prior to lethal ischemia does not influence the degree of the secondary ischemic insult. However it may have some effect on cellar organ molecular activity like a mitochondrial enzyme PDH,and influences protein synthesis in CA_1 region, which may be essentials to induce ischemic tolerance. Less