Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury

In this study, the metabolic, enzymatic and gene changes causing cerebral glucose dysmetabolism followinggraded diffuse traumatic brain injury (TBI) were evaluated. TBI was induced in rats by dropping 450 g from 1(mild TBI; mTBI) or 2 m height (severe TBI; sTBI). After 6, 12, 24, 48, and 120 h gene expressions and enzymaticactivities of glycolysis and pentose phosphate pathway (PPP) enzymes, and levels of lactate, ATP, ADP, ATP/ADP(indexing mitochondrial phosphorylating capacity), NADP+, NADPH and GSH were determined in whole brainextracts (n = 9 rats at each time for both TBI levels). Sham-operated animals (n = 9) were used as controls.Results demonstrated that mTBI caused a late increase (48–120 h post injury) of glycolytic gene expressionand enzymatic activities, concomitantly with mitochondrial functional recovery (ATP and ATP/ADP normalization).No changes in lactate and PPP genes and enzymes, were accompanied by transient decrease in GSH,NADP+, NADPH and NADPH/NADP+. Animals following sTBI showed early increase (6–24 h post injury) of glycolyticgene expression and enzymatic activities, occurring during mitochondrial malfunctioning (50% decreasein ATP and ATP/ADP). Higher lactate and lower GSH, NADP+, NADPH, NADPH/NADP+ than controls wererecorded at anytime post injury (p b 0.01). Both TBI levels caused metabolic and gene changes affecting glucosemetabolism. Following mTBI, increased glucose flux through glycolysis is coupled to mitochondrial glucoseoxidation. “True” hyperglycolysis occurs only after sTBI, where metabolic changes, caused by depressed mitochondrialphosphorylating capacity, act on genes causing net glycolytic flux increase uncoupled from mitochondrialglucose oxidation.