Glycolysis and pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-13C2 glucoseReport as inadecuate


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


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Publication Date: 2014-10-22

Journal Title: Journal of Cerebral Blood Flow & Metabolism

Publisher: Nature Publishing Group

Volume: 35

Pages: 111-120

Language: English

Type: Article

Metadata: Show full item record

Citation: Jalloh, I., Carpenter, K. L. H., Grice, P., Howe, D. J., Mason, A., Gallagher, C. N., Helmy, A., et al. (2014). Glycolysis and pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-13C2 glucose. Journal of Cerebral Blood Flow & Metabolism, 35 111-120.

Description: This is the accepted manuscript version. The final version is available from the Nature Publishing Group http://www.nature.com/jcbfm/journal/v35/n1/full/jcbfm2014177a.html.

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 1,2-13C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in 6 patients undergoing surgery for benign tumours, and to simultaneously collect products for NMR analysis. 13C enrichment for glycolytic 2,3-13C2 lactate was median 5.4% (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 3-13C lactate to glycolytic 2,3-13C2 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 vs. 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.

Keywords: 13C-labelling, glycolysis, pentose phosphate pathway, lactate, traumatic brain injury (human)

Sponsorship: 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.

Identifiers:

This record's URL: http://www.repository.cam.ac.uk/handle/1810/245936http://dx.doi.org/10.1038/jcbfm.2014.177





Author: Jalloh, IbrahimCarpenter, Keri L. H.Grice, PeterHowe, Duncan J.Mason, AndrewGallagher, Clare N.Helmy, AdelMurphy, Michael P.Menon,

Source: https://www.repository.cam.ac.uk/handle/1810/245936



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