1091: DISCOVERY OF LIPIDOME ALTERATIONS AFTER PEDIATRIC SEVERE TRAUMATIC BRAIN INJURY

Introduction: Pediatric traumatic brain injury (TBI) is a leading cause of childhood disability and mortality, with no currently approved therapies shown to improve outcomes. We hypothesized that metabolomics analysis would demonstrate novel insights into pediatric TBI pathophysiology. Methods: After IRB approval (CWH 2021-096) and informed consent, seventeen pediatric severe TBI patients ages ≥ 1 and ≤ 21 years were prospectively enrolled along with 10 matched controls. Serial blood samples were collected at 24 ± 12 hours (timepoint 1), 48 ± 12 hours (timepoint 2), and on hospital day 9 ± 12 (timepoint 3) hours. Demographics and clinical variables were extracted from the medical record. Targeted metabolomic serum profiling was performed using high-resolution liquid chromatography–tandem mass spectrometry (LC-MS/MS), proton magnetic resonance (H NMR). Data were analyzed using machine learning methods. Results: Metabolomic profiling revealed unique temporal changes after TBI, with Principal Component Analysis (PCA) demonstrating clustering of data at timepoints 1 and 2, and unique data clustering at timepoint 3. TBI profiles were unique from controls. Early timepoints showed significant elevation in levels of phosphatidylcholines (PC), polyunsaturated fatty acids (PUFA), and triglycerides (TG), with decrease in monounsaturated fatty acid levels. The later timepoint demonstrated significant increases in sphingomyelins (SM) and ceramides. Lipid levels correlated with severity scores such as PRISM III and recovery scores such as GOS-E Peds scores. Conclusions: Changes in microglial lipid composition have been described in pre-clinical TBI models in the blood and brain. Blood based lipidomic changes in rodents and adults have been associated with severity measures, and chronic lipid perturbations associated with long-term cognitive dysfunction. However a paucity of data in children remains. Understanding temporal changes in peripheral lipidomics may provide valuable diagnostic and prognostic insights into acute and chronic TBI pathophysiology in the developing brain.