Advances in metabolomics of biomarkers for ischemic stroke: From bench to clinic

Ischemic stroke, a neurological impairment caused by cerebral vascular occlusion, accounts for 87% of the cases of stroke. Recent studies have shown that changes in the abundance of metabolites can directly reveal the cellular phenotypes and identify the clinical implications of stroke diagnosis and therapy. However, systematic research to clarify the relationship between biomarkers and the mechanisms of ischemic stroke remains limited. In this study, we reviewed articles on ischemic stroke metabolites from 2005 to 2024, identified metabolites showing significant changes, and constructed a metabolite database based on the findings from 128 studies. The database included 125 differential metabolites detected in a middle cerebral artery occlusion mouse model, 246 detected in an middle cerebral artery occlusion rat model, and 764 identified in ischemic stroke patient samples. Differential metabolites from various samples were then screened and classified into positive and negative categories based on their correlation with stroke prognoses. Based on this analysis, three positive metabolites and two negative metabolites were identified. Glutamic acid, glycerol, and 1-octadecanoyl-sn-glycero-3-phosphocholine (LysoPC(18:0)) were further recognized as potential biomarkers. Imbalances in metabolic pathways such as alanine, aspartate, and glutamate metabolism as well as the citrate cycle (tricarboxylic acid cycle) were analyzed. These imbalances may influence the pathogenesis of ischemic stroke by altering biological processes such as excitotoxicity, oxidative stress, inflammation, and energy metabolism. The identification and analysis of these potential biomarkers may provide valuable targets and strategies for prediction, diagnosis, and prognostic assessment of ischemic stroke.