Ischemic tolerance phenomenon from an approach of energy metabolism and the mitochondrial enzyme activity of pyruvate dehydrogenase in gerbils.

The objective of this study was to determine if the pretreatment with a sublethal ischemic insult, which has been shown to protect against delayed neuronal death, effects the recovery of energy metabolites or alters the activity of pyruvate dehydrogenase (PDH) following transient cerebral ischemia. Gerbils were pretreated with a sublethal ischemic insult, 2 min of bilateral common carotid artery occlusion, and 24 h later given a 5-min lethal ischemic insult. Animals were reperfused for 0, 10, or 60 min, or 1, 3 or 7 days. Brain metabolites, ATP, PCr, and lactate, and PDH activity were measured in the cortex and the hippocampal CA1 region. The pretreatment had no effect on ATP and PCr depletion or on lactate accumulation after the 5-min insult, nor on their recovery up to 1 day reperfusion, although there was a difference in the lactate levels of the non-pretreated and the pretreated gerbils after 10 min reperfusion. The pretreatment also had no effect on PDH activity during ischemia and reperfusion in either region. However, at 3 days reperfusion the non-pretreated animals exhibited a secondary decrease in ATP levels in the hippocampus. At 7 days reperfusion, ATP levels in the hippocampus of both the pretreated animals and the non-pretreated animals were significantly decreased compared to controls. Additionally, the level of ATP in the non-pretreated group was significantly lower than that in the pretreated group. The pretreatment with a sublethal ischemic insult did not effect the initial recovery of metabolites or the activity of PDH following transient cerebral ischemia. However, it protected against the secondary decrease of ATP levels in the hippocampus. Thus, the induction of ischemic tolerance is not caused by a reduction in metabolic impairment during the secondary insult.