Abstract TP236: Temporal Metabolomic Profiling Exposed Affiliated Metabolites Altered And Associations To Outcome After Different Acute Brain Injuries

Background: Neuronal recovering processes after acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI) are complex including brain plasticity and synaptic regeneration mechanisms. Hypotheses: Transient changes in metabolome after different acute brain injuries may reveal affiliated metabolites, metabolic pathways and associations that can also reflect important biological mechanisms. Measurable temporal changes in serum metabolomic profile may be similar irrespective of the type of the brain injury. These metabolomic commonalities may be associated to outcome. Methods: Prospective cohort (n=74) consisted of IS (n=30), aSAH (n=31) and TBI (n=13) patients. Serum samples were collected in two time points after the insult (early 24-48h and late 120-192h). Orbitrap Profiling of 462 metabolites was used to measure metabolites. Outcome was measured 90 days after injury (mRS favorable 0-3, unfavorable 4-6). The metabolomics data was imputed for missing value using KNN with 20% cut off for missing value, log-transformed and autoscaled. For statistics, t-test and ANOVA was performed and FDR-corrected p-value 0.05 was considered to be statistically significant. Results: We identified four similarly temporally increased metabolite levels across all acute brain injury types (p<0.05, FDR corrected). Twenty-eight metabolites were shown to have similar trend when only IS and TBI groups were compared. Whereas outcome analysis showed three metabolites associating both favorable and unfavorable outcome across all acute brain injury types (p<0,05, FDR corrected). IS and TBI groups combined twenty common metabolites were identified to associate favorable and twenty-three with unfavorable outcome (p<0,05, FDR corrected). Conclusion: Similar metabolic changes across time were identified with apparent associations to outcome. This suggests important common metabolic characteristics irrespective of the type of brain insult and encourage further studies and validation. Identified metabolites may be further developed as a prognostic biomarker and may indicate new metabolic pathways active irrespective the type of brain injury reflecting biological mechanisms.