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


Type

Article

Change log

Authors

Jalloh, Ibrahim 
Carpenter, Keri LH 
Howe, Duncan J 
Mason, Andrew 

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.

Description

Keywords

Adolescent, 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

Journal Title

J Cereb Blood Flow Metab

Conference Name

Journal ISSN

0271-678X
1559-7016

Volume Title

35

Publisher

Nature Publishing Group
Sponsorship
Medical Research Council (G0600986)
Medical Research Council (G1002277)
TCC (None)
Medical Research Council (G0802251)
Medical Research Council (G0001354)
Medical Research Council (G9439390)
Medical Research Council (MC_U105663142)
Medical Research Council (G1000183)
Medical Research Council (G0600986/1)
Medical Research Council (G0802251/1)
Medical Research Council (G1002277/1)
We gratefully acknowledge financial support as follows. Study support: Medical Research Council (Grant Nos. G0600986 ID79068 and G1002277 ID98489) and National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Authors’ support: I.J. – Medical Research Council (Grant no. G1002277 ID 98489) and National Institute for Health Research Biomedical Research Centre, Cambridge; K.L.H.C. – National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); C.G. – the Canadian Institute of Health Research; A.H. – Medical Research Council/ Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no. G0802251) and Raymond and Beverly Sackler Fellowship; D.K.M. and J.D.P. - National Institute for Health Research Senior Investigator Awards; P.J.H. – National Institute for Health Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship.