Abstract WP349: Systemic Metabolic Alterations in Intracerebral Hemorrhage Identified via NMR-Based Serum Metabolomics

Introduction: Intracerebral hemorrhage (ICH) is a severe and often fatal stroke subtype affecting 2 million people worldwide each year. Although well defined by neuroimaging, biological changes leading to ICH or resulting from ICH are not well understood. This leads to poor patient outcomes. In this pilot study, we used serum metabolomics to identify small-molecule biomarkers associated with ICH to better understand ICH occurrence and metabolism. Hypothesis: We hypothesized that ICH would have specific metabolomic profiles compared to controls. Methods: Using the Nuclear Magnetic Resonance (NMR) platform, we evaluated 250 serum metabolites from a cohort of 23 patients with ICH and 86 controls. Metabolite levels between ICH and controls were compared using a two-sided two-sample equal-variance t-test. These metabolites included various lipoprotein classes, amino acids, ketones, and energy metabolites. We used the Two-Stage Benjamini&Hochberg (TSBH) procedure for multiple testing. Results: Metabolomic analysis revealed significant alterations in 125 metabolites between the control and hemorrhagic groups. Notably, levels of different lipoprotein classes and phospholipids (Phosphoglycerides and Phosphatidylcholine), important components of nerve cell membranes, were significantly reduced in the hemorrhagic group compared to controls (TSBH p ≤ 0.01) (Table 1). In addition, concentrations of alanine and histidine were also reduced in ICH patients. In contrast, pyruvate levels in the hemorrhagic group were elevated. Conclusion: Our findings highlight systemic metabolic disturbances associated with hemorrhagic stroke. Decreased concentration of nerve cell membrane components may reflect predisposition of patients to the index ICH event, while an increase in pyruvate may reflect a shift toward anaerobic metabolism. Future larger-scale studies should validate these interesting findings and associate them with patients’ outcomes.