A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.
Authors
Jalloh, Ibrahim
Howe, Duncan J
Shannon, Richard J
Mason, Andrew
Gallagher, Clare N
Publication Date
2018-09-01Journal Title
J Neurotrauma
ISSN
0897-7151
Publisher
Mary Ann Liebert Inc
Volume
35
Issue
17
Pages
2025-2035
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Jalloh, I., Helmy, A., Howe, D. J., Shannon, R. J., Grice, P., Mason, A., Gallagher, C. N., et al. (2018). A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.. J Neurotrauma, 35 (17), 2025-2035. https://doi.org/10.1089/neu.2017.5459
Abstract
Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-13C lactate metabolism in TBI with "normal" control brain and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3-13C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-13C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain. 13C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-13C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."
Keywords
Humans, Lactic Acid, Glutamine, Dialysis, Magnetic Resonance Spectroscopy, Brain Chemistry, Citric Acid Cycle, Oxidation-Reduction, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Brain Injuries, Traumatic
Sponsorship
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: IJ – Medical Research Council (Grant no. G1002277 ID 98489) and National Institute for Health Research Biomedical Research Centre, Cambridge; KLHC – National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); CG – the Canadian Institute of Health Research; AH – Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no. G0802251) and Raymond and Beverly Sackler Fellowship; Royal College of Surgeons of England and the NIHR Cambridge Biomedical Research Centre; DKM and JDP – National Institute for Health Research Senior Investigator Awards; MPM - Medical Research Council UK (MC_U105663142) and a Wellcome Trust Investigator award (110159/Z/15/Z). PJH – National Institute for Health Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship and the National Institute for Health Research Biomedical Research Centre, Cambridge.
Funder references
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Royal College of Surgeons of England (2016/2017)
Medical Research Council (G0001237)
Medical Research Council (G9439390)
Medical Research Council (G0600986)
Medical Research Council (G1002277)
Wellcome Trust (110159/Z/15/Z)
Medical Research Council (MC_UU_00015/3)
Medical Research Council (MC_U105663142)
Medical Research Council (G0802251)
NETSCC (None)
TCC (None)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1089/neu.2017.5459
This record's URL: https://www.repository.cam.ac.uk/handle/1810/278188
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