New insights into metabolism dysregulation after TBI

Abstract

Traumatic brain injury (TBI) remains a leading cause of death and disability that places a great physical, social, and financial burden on individuals and the health system. In this review, we summarize new research into the metabolic changes described in clinical TBI trials, some of which have already shown promise for informing injury classification and staging. We focus our discussion on derangements in glucose metabolism, cell respiration/mitochondrial function and changes to ketone and lipid metabolism/oxidation to emphasize potentially novel biomarkers for clinical outcome prediction and intervention and offer new insights into possible underlying mechanisms from preclinical research of TBI pathology. Finally, we discuss nutrition supplementation studies that aim to harness the gut/microbiome-brain connection and manipulate systemic/cellular metabolism to improve post-TBI recovery. Taken together, this narrative review summarizes published TBI-associated changes in glucose and lipid metabolism, highlighting potential metabolite biomarkers for clinical use, the cellular processes linking these markers to TBI pathology as well as the limitations and future considerations for TBI "omics" work.

Keywords: Glucose metabolism; Gut-brain axis; Ketometabolism; Lipid oxidation; Microbiome; Mitochondrial metabolism.

Fig. 1

Cellular metabolism dysregulation in TBI. TBI-induced changes of canonical glucose metabolism including increased reliance on lactate and glycolytic metabolism, lipid derived metabolites, increased oxidative stress, inflammation and altered mitochondrial function are schematically displayed. ATP: Adenosine triphosphate; BBB: Blood Brain Barrier leakage; BCAA: Branched Chain Amino Acid; GLUTs: Glucose transporters; Cyt C: Cytochrome C; FAD: Flavin adenine dinucleotide; NAD: Nicotinamide adenine dinucleotide; Nrf2: Nuclear factor erythroid 2-related factor 2; PLA2: Phospholipase A2; ROS: Reactive Oxygen Species; Sirt1: Sirtuin 1