title: Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose.
abstract: Increased 'anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-(13)C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. (13)C enrichment for glycolytic 2,3-(13)C2 lactate was the median 5.4% (interquartile range (IQR) 4.6-7.5%) in TBI brain and 4.2% (2.4-4.4%) in 'normal' brain (P<0.01). The ratio of PPP-derived 3-(13)C lactate to glycolytic 2,3-(13)C2 lactate was median 4.9% (3.6-8.2%) in TBI brain and 6.7% (6.3-8.9%) in 'normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=-0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than 'normal' brain. Several TBI patients exhibited PPP-lactate elevation above the 'normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain.
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Jalloh
authors.affiliation: 1] Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Keri L H
authors.initials: KL
authors.lastname: Carpenter
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Grice
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Howe
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mason
authors.affiliation: 1] Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Division of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Clare N
authors.initials: CN
authors.lastname: Gallagher
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Adel
authors.initials: A
authors.lastname: Helmy
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: 1] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: T Adrian
authors.initials: TA
authors.lastname: Carpenter
authors.affiliation: 1] Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: John D
authors.initials: JD
authors.lastname: Pickard
authors.affiliation: 1] Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hutchinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002247:Carbon Isotopes; D016022:Case-Control Studies; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D010427:Pentose Phosphate Pathway; D055815:Young Adult
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D005947:Glucose