Effect of duration of cerebral ischemia on pyruvate dehydrogenase activity (PDH) and metabolites in the gerbil brain

Abstract

Pyruvate dehydrogenase (PDH) is one of the mitochondrial enzymes which regulate the glucose metabolism. The purpose of this study is to determine the effect of the duration of cerebral ischemia on PDH activity and the metabolites. Cerebral ischemia was produced by bilateral common carotid artery occlusion in Mongolian Gerbils. 20-minute (1) and 60-minute ischemic groups (2) were made. PDH activity and energy metabolites (ATP, PCr, lactate) were measured in the caudate nucleus and cortex at each time period. 1) 20 min ischemic group: PDH activity significantly increased after 20-min ischemia in both the caudate nucleus and cortex, and decreased to levels less than that of the control after 20 min reperfusion. At 60 and 120 min reperfusion, PHD activity returned to the control levels. ATP and PCr concentrations were significantly depleted after the ischemic insult, returning to 60-80% of the control level after reperfusion. Lactate concentrations increased significantly after ischemia, and were reduced by reperfusion. 2) 60 min ischemic group: PDH activity significantly increased after 60 min ischemia, and decreased but remained higher than the control level after 20 min reperfusion. At 60 and 120 min reperfusion, PDH activity gradually decreased towards control levels. ATP and PCr concentrations were depleted after ischemia, and were gradually restored after 20 min reperfusion, recovering to 50% after 60 min reperfusion. Lactate concentrations increased after the ischemic insult, and became more elevated after reperfusion. These findings indicate that there is a significant difference in the PDH activity and metabolism depending on the duration of ischemia. The data suggest that impaired metabolism and persistent elevation of PDH activity may be caused by damage to the mitochondria allowing the influx of Ca2+ during prolonged ischemia.