title: Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury.
abstract: 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 450g from 1 (mild TBI; mTBI) or 2m height (severe TBI; sTBI). After 6, 12, 24, 48, and 120h 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 (48-120h 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 (6-24h 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<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.
authors: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Largo F. Vito 1, 00168 Rome, Italy. Electronic address: angela.amorini@rm.unicatt.it.
authors: Angela Maria
authors: AM
authors: Amorini
authors: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Largo F. Vito 1, 00168 Rome, Italy. Electronic address: g.lazzarino@libero.it.
authors: Giacomo
authors: G
authors: Lazzarino
authors: Neurobiology, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, B15 2TT Birmingham, UK. Electronic address: v.dipietro@bham.ac.uk.
authors: Valentina
authors: V
authors: Di Pietro
authors: Division of Neurosurgery, Department of Neurosciences Head and Neck Surgery, S. Camillo Hospital, Circonvallazione Gianicolense 87, 00152 Rome, Italy. Electronic address: stefano.signoretti@tiscali.it.
authors: Stefano
authors: S
authors: Signoretti
authors: Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. Electronic address: lazzarig@unict.it.
authors: Giuseppe
authors: G
authors: Lazzarino
authors: Neurobiology, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, B15 2TT Birmingham, UK; National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, B15 2TH Birmingham, UK. Electronic address: a.belli@bham.ac.uk.
authors: Antonio
authors: A
authors: Belli
authors: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Largo F. Vito 1, 00168 Rome, Italy. Electronic address: btavazzi@rm.unicatt.it.
authors: Barbara
authors: B
authors: Tavazzi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009419:Nerve Tissue Proteins; D005947:Glucose
keywords: Energy metabolism; Glucose dysmetabolism; Glycolysis; Mitochondrial dysfunction; Pentose phosphate pathway; Traumatic brain injury