Understanding and ameliorating perturbations of human cerebral energy metabolism after major trauma
University of Cambridge
Doctor of Philosophy (PhD)
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Stovell, M. (2021). Understanding and ameliorating perturbations of human cerebral energy metabolism after major trauma (Doctoral thesis). https://doi.org/10.17863/CAM.70621
After sustaining a severe traumatic brain injury (TBI) dysfunction of cerebral energy metabolism can cause further injury to the traumatised brain – resulting in worse patient morbidity, or death. Using the modalities of cerebral microdialysis, 13C labelled high-resolution nuclear magnetic resonance (NMR) and in-vivo 31P magnetic resonance spectroscopy (MRS) I have furthered our understanding of perturbations in human brain energy metabolism in the acute phase of a major traumatic brain injury. Furthermore, I have explored whether increasing the amount or changing the type of substrate available to the traumatised brain improves its energy metabolism. Study I (Chapter 3): I studied the effect of supplementing the traumatised human brain with glucose at high-physiological and supra-physiological concentrations. Study II (Chapter 4): I defined the optimum parameters for acquiring and analysing in-vivo 31P magnetic resonance spectra in acute TBI patients. Study III (Chapter 5): I studied the effect of acute major TBI on brain energy state and ‘whole brain’ pH using 31P magnetic resonance spectroscopy, and how this relates to patient outcome. Study IV (Chapter 6): I studied the effect of sodium succinate supplementation to the traumatised brain’s energy state using 31P magnetic resonance spectroscopy, and how this relates to the brain’s extracellular ratio of lactate to pyruvate. Study V (Chapter 7): I studied the diffusion of small molecules from cerebral microdialysis catheters in the human brain using a gadolinium-based contrast agent and magnetic resonance imaging. The findings of these studies change our understanding of energy metabolism in the acutely traumatised human brain, which may also translate to that of the healthy human brain. They prompt the development of new clinical tools to aid prognostication, and guide potential clinical trials of metabolic therapies in the future.
Traumatic brain injury, TBI, Cerebral energy metabolism, Microdialysis, Magnetic resonance spectroscopy
Medical Research Council (Grant No G1002277 ID98489). National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme) and NIHR Brain Injury Healthcare Technology Co-operative (Supported Project 2016/17).
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This record's DOI: https://doi.org/10.17863/CAM.70621
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