Ischemic stroke is a leading cause of mortality and long-term disability. Despite advances in reperfusion therapies, clinical outcomes remain highly variable, underscoring the need for improved molecular understanding of the disease. In this study of a Croatian clinical cohort, high-resolution untargeted UHPLC–MS/MS metabolomics was performed on serum samples from 14 ischemic stroke patients and 14 controls, as well as on retrieved cerebral thrombi. After quality-control assessment, paired thrombus–serum analysis included 11 matched pairs and revealed a distinct thrombus-associated metabolic profile characterized by identified metabolites related to amino acid metabolism and pyrimidine turnover, together with putatively annotated features suggestive of nucleotide turnover and membrane phospholipid remodeling. In contrast, patient–control serum comparisons revealed putatively annotated metabolic features consistent with altered amino acid metabolism and redox-related processes associated with the systemic response to acute ischemia. Metabolic profiling of retrieved thrombi revealed candidate biochemical signatures suggestive of platelet activation, cellular breakdown, and membrane remodeling that are not fully captured in blood alone. Overall, this integrated metabolomics approach supports the concept of distinct systemic and thrombus-associated metabolic remodeling in acute ischemic stroke and highlights candidate metabolic features and pathways for future targeted validation and integration with thrombus composition, reperfusion characteristics, and clinical outcomes.
Karmelić et al. (2026) studied this question.