In this study, the metabolic, enzymatic and gene changes causing cerebral glucose dysmetabolism following graded 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 enzymatic activities 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 brain extracts (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 expression and 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 glycolytic gene expression and enzymatic activities, occurring during mitochondrial malfunctioning (50% decrease in ATP and ATP/ADP). Higher lactate and lower GSH, NADP+, NADPH, NADPH/NADP+ than controls were recorded at anytime post injury (p b 0.01). Both TBI levels caused metabolic and gene changes affecting glucose metabolism. Following mTBI, increased glucose flux through glycolysis is coupled to mitochondrial glucose oxidation. “True” hyperglycolysis occurs only after sTBI, where metabolic changes, caused by depressed mitochondrial phosphorylating capacity, act on genes causing net glycolytic flux increase uncoupled from mitochondrial glucose oxidation.
|Titolo:||Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury|
|Data di pubblicazione:||2016|
|Citazione:||Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury / Amorini AM; Lazzarino Giacomo; Di Pietro V; Signoretti S; Lazzarino G; Belli A; Tavazzi B. - In: BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE. - ISSN 0925-4439. - 1862(2016), pp. 679-687.|
|Appare nelle tipologie:||1.1 Articolo in rivista|