Lundgren J, Cardell M, Wieloch T, Siesjö B K
Laboratory for Experimental Brain Research, University of Lund, Lund Hospital, Sweden.
J Cereb Blood Flow Metab. 1990 Jul;10(4):536-41. doi: 10.1038/jcbfm.1990.95.
Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total PDHC activity were measured in neocortical samples as the rate of decarboxylation of [14C]pyruvate in crude brain mitochondrial homogenates after 5 min, 15 min, 1 h, 6 h, and 18 h of recirculation following 15 min of incomplete cerebral ischemia. In normoglycemic animals the fraction of activated PDHC, which rises abruptly during ischemia, was reduced to 19-25% during recirculation compared with 30% in sham-operated controls. In hyperglycemic rats the fraction of activated PDHC was higher during the first 15 min of recirculation. However, after 1 and 6 h of recirculation, the fraction was reduced to values similar to those measured in normoglycemic animals. Fifteen of 26 rats experienced early (1-4 h post ischemia) seizures in the recovery period. The PDHC activity appeared unchanged prior to these early postischemic seizures. We conclude that the accentuated depression of postischemic metabolic rate observed in hyperglycemic animals is not coupled to a corresponding postischemic depression of PDHC.(ABSTRACT TRUNCATED AT 250 WORDS)
血糖正常的动物发生短暂性脑缺血后，葡萄糖利用率降低，这反映了缺血后脑代谢抑制以及丙酮酸脱氢酶复合体（PDHC）活性降低。缺血前高血糖会加重缺血性脑损伤并总是引发癫痫，已知其会进一步降低脑代谢率。为了研究这些效应是否伴随着PDHC活性的变化，我们在缺血前高血糖（血浆葡萄糖20 - 25 mM）的大鼠中研究了该酶的缺血后脑皮质活性。将结果与血糖正常的动物（血浆葡萄糖5 - 10 mM）所得结果进行比较。在不完全性脑缺血15分钟后再灌注5分钟、15分钟、1小时、6小时和18小时后，在新皮质样本中测量PDHC的活化部分和总PDHC活性，以粗制脑线粒体匀浆中[14C]丙酮酸的脱羧速率来表示。在血糖正常的动物中，缺血期间突然升高的活化PDHC比例，在再灌注期间降至19 - 25%，而假手术对照组为30%。在高血糖大鼠中，再灌注的前15分钟活化PDHC比例较高。然而，再灌注1小时和6小时后，该比例降至与血糖正常动物中测得的值相似。26只大鼠中有15只在恢复期出现早期（缺血后1 - 4小时）癫痫发作。在这些早期缺血后癫痫发作之前，PDHC活性似乎未发生变化。我们得出结论，在高血糖动物中观察到的缺血后代谢率的加重抑制与PDHC相应的缺血后抑制并无关联。（摘要截选至250字）
