Brain lactate during partial global ischemia and reperfusion: effect of pretreatment with dichloroacetate in a rat model.
Elevated cerebral lactate levels following cerebral ischemia have been associated with brain cell damage and death. We previously found that pre- or postischemia treatment with dichloroacetate (DCA), presumably by its activation of brain pyruvate dehydrogenase, effectively lowers cerebral lactate levels in rats subjected to 30 minutes of partial global ischemia (PGI) followed by 30 minutes of recirculation. The goal of the present study was to determine the effects of preischemia DCA treatment on cortical lactate levels during the ischemia period or during early recirculation. Rats (four in each group) received preischemia treatment with DCA and were then subjected to 0, 10, or 30 minutes of PGI or 30 minutes of PGI followed by 15 minutes of recirculation. Cortical lactate levels in pretreated animals were not significantly different from lactate levels of untreated rats at any time during PGI, but were significantly lower than levels in untreated rats at 15 minutes of recirculation (P less than .05, ANOVA). These results suggest that preischemia treatment with DCA does not limit the accumulation of cortical lactate during PGI but may promote its clearance during recirculation following PGI. If reperfusion events influence the degree of brain cell injury, DCA may enhance cell recovery by lower cortical lactate levels in the reperfusion period.
D000085:Acetates / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D002540:Cerebral Cortex / Q000378:metabolism; D002560:Cerebrovascular Circulation; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007773:Lactates / Q000097:blood / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000085:Acetates; D001786:Blood Glucose; D007773:Lactates; D006003:Glycogen; D003999:Dichloroacetic Acid; D005947:Glucose