Abstract WP025: Erythrocyte Metabolic Signatures in Ischemic Stroke: Early Predictive Markers for Disease Severity and Functional Outcomes

Objective: Microcirculatory ischemia and hypoxia are key drivers in the pathological progression of ischemic stroke (IS). As the primary carriers of oxygen transport, erythrocytes and their metabolic adaptive changes in IS have not been systematically elucidated. This study aims to explore the association between erythrocyte and plasma metabolomic profiles and the pathogenesis of IS, and to evaluate the potential clinical value of key metabolites as biomarkers for disease diagnosis, NIHSS score (indicating severity), and mRS score (assessing 90-day functional outcomes). Methods: A case-control design was adopted, including 110 patients with acute IS (AIS group) and 70 healthy controls (HC group). Untargeted metabolomic analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect erythrocyte and plasma metabolic profiles. Multivariate statistical analysis (PLS-DA) was employed to screen differential metabolites, and Spearman correlation analysis was used to assess the relationship between metabolite levels and NIHSS/mRS scores. Results: A total of 148 differentially expressed metabolites were identified in erythrocytes between AIS and HC groups, of which 38 were significantly correlated with NIHSS scores and 28 with mRS scores. In plasma, 193 differential metabolites were detected, with 58 associated with NIHSS scores and 37 with mRS scores. Ten metabolites showed significant correlations with NIHSS scores in both erythrocytes and plasma, while five metabolites were correlated with mRS scores in both sample types. A key finding was that five metabolites-capric acid, 2-hydroxybutyric acid, ricinoleic acid, dodecanoic acid, and L-serine—were significantly correlated with both NIHSS and mRS scores across both sample types. Conclusion: This study is the first to report the association between erythrocyte metabolic reprogramming and clinical outcomes in IS, confirming that five metabolites, including capric acid, can serve as multi-functional biomarkers across omics dimensions.