Investigation of the impact of experimental Traumatic Brain Injury on acute changes in immuno-metabolism gene expression in the mouse cortex and hippocampus. Susan C. Burke1, Yvonne M. Nolan1,2, Harriet Schellekens1,2, Rebecca J. Henry1 1. Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland 2. APC Microbiome Ireland, University College Cork, Cork, Ireland Introduction: Neuroinflammation is a key secondary injury mechanism following exposure to traumatic brain injury (TBI). Evidence suggests that shifts in intracellular metabolic processes (oxidative phosphorylation → glycolysis) drives pro-inflammatory responses in the brain microenvironment. Thus, the aim of the present study was to examine acute changes in expression of inflammatory and metabolic genes in the cortex and hippocampus following exposure to TBI. Methodology: Adult male C57BL/6 mice (n=5) underwent either moderate level controlled cortical impact (CCI) or sham surgery. Mice were euthanised at 7 days post injury (dpi) and ipsilateral cortical and hippocampal tissue was processed for mRNA analysis. Statistical analysis was preformed using an unpaired Student’s t-test. Results: TBI resulted in a significant increase in cortical expression of the pro-inflammatory mediators NLRP3 (p<0.01), IL-1β (p<0.01), TNF-α (p<0.001), NOX-2 (p<0.05), and p22phox (p<0.01), when compared to sham operated counterparts. Similar effects were reported in the hippocampus including significant TBI-induced increases in NLRP3 (p<0.01), IL-1β (p<0.001), TNF-α (p<0.0001), NOX-2 (p<0.05), and p22phox (p<0.01). In addition, TBI resulted in a significant increase in both cortical (p<0.05) and hippocampal (p<0.001) expression of the microglial marker, CD11b, when compared to sham counterparts. TBI resulted in a significant increase in cortical (p<0.001) and hippocampal (p<0.0001) expression of the master regulator of glycolysis, PFKFB3. Furthermore, TBI resulted in a significant increase in hippocampal (p<0.01), but not cortical expression of PFKFB1. Finally, TBI did not significantly alter gene expression of markers associated with oxidative phosphorylation including PGC1α and SIRT-1 in the cortex or hippocampus. Conclusions: Exposure to TBI results in acute increases in cortical and hippocampal pro-inflammatory gene expression and select markers of glycolytic metabolism. Developing our understanding of immuno-metabolic responses following exposure to TBI may offer novel insights into therapeutic targets. Page | 54