Metabolic profiling of traumatic brain injury, associated outcomes and treatment in rodents
File(s)
Author(s)
Valeo, Flavia
Type
Thesis or dissertation
Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Due to major lacks in diagnostic and treatment measures, there is a need to identify biomarkers of TBI that could aid in improving TBI management. The main goal of this thesis was to characterise the metabolic profiles of rodent TBI to improve knowledge of the metabolic responses of TBI and treatment with xenon, ultimately aiding in biomarker identification. Using a rat model of blunt TBI and untargeted metabolomics, the thesis first looked at identifying plasma metabolic changes related to multiple TBI severity in the acute phase (15 minutes and 24 hours post-injury). Second, the thesis investigated the acute plasma metabolic responses of severe TBI and treatment with xenon gas, to identify biomarkers of severe TBI and xenon’s neuroprotective effect. To conclude, integration of metabolic profiles of severe TBI and TBI-related motor (i.e., gait) and histological outcomes (i.e., neuronal density) was conducted to identify the specificity of TBI metabolic responses with brain injury deficits. The thesis first identified an association between N-acetyl glycoproteins with TBI injury severity at 24 hours post-injury (pFDR = 0.024). Additionally, a plasma metabolic signature comprising of purine and pyrimidine metabolites were identified to be altered in severe TBI, particularly the alteration in plasma urate compared to sham animals (pFDR = 0.064). Multivariate modelling of the overall TBI-related metabolome also identified a trend in xenon’s ability to positively affect the TBI-related metabolome (p = 0.0082). Finally, an association between the identified metabolic profiles of severe TBI, neuronal density (pFDR < 0.1) and gait impairment (pFDR < 0.1) was identified. These findings, alongside the analytical pipeline applied, serve as the basis for future studies towards the identification of diagnostic, prognostic and therapeutic TBI biomarkers.
Version
Open Access
Date Issued
2022-03
Date Awarded
2023-03
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Dickinson, Robert
Dumas, Marc-Emmanuel
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)