Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose.

TitleGlycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose.
Publication TypeJournal Article
Year of Publication2015
AuthorsJalloh, I, Carpenter, KLH, Grice, P, Howe, DJ, Mason, A, Gallagher, CN, Helmy, A, Murphy, MP, Menon, DK, T Carpenter, A, Pickard, JD, Hutchinson, PJ
JournalJ Cereb Blood Flow Metab
Volume35
Issue1
Pagination111-20
Date Published2015 Jan
ISSN1559-7016
KeywordsAdolescent, Adult, Aged, Brain, Brain Injuries, Carbon Isotopes, Case-Control Studies, Female, Glucose, Glycolysis, Humans, Lactic Acid, Magnetic Resonance Spectroscopy, Male, Microdialysis, Middle Aged, Pentose Phosphate Pathway, Young Adult
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.

DOI10.1038/jcbfm.2014.177
Alternate JournalJ. Cereb. Blood Flow Metab.
Citation Key10.1038/jcbfm.2014.177
PubMed ID25335801
PubMed Central IDPMC4294402
Grant List113 / / Department of Health / United Kingdom
G0600986 / / Medical Research Council / United Kingdom
G0600986 / / Medical Research Council / United Kingdom
G0802251 / / Medical Research Council / United Kingdom
G0802251 / / Medical Research Council / United Kingdom
G1000183B / / Medical Research Council / United Kingdom
G1002277 / / Medical Research Council / United Kingdom
G1002277 / / Medical Research Council / United Kingdom
MC_U105663142 / / Medical Research Council / United Kingdom
NF-SI-0508-10327 / / Department of Health / United Kingdom
NIHR-RP-R3-12-013 / / Department of Health / United Kingdom
/ / Canadian Institutes of Health Research / Canada