Analysis of ischemic stroke biomarkers based on non-targeted metabolomics

Biomarkers for ischemic stroke (IS) are yet to fulfill clinical requirements. This study used non-targeted metabolomics to investigate differential metabolites and metabolic pathways in plasma and brain tissue following IS, with the aim of identifying new potential biomarkers and therapeutic targets. Twelve Tibetan miniature pigs were randomly assigned to a model- or sham-operation group. An electrocoagulation-based anterior temporal approach was employed to occlude the middle cerebral artery, thereby creating a model for IS. Plasma and brain tissue samples were collected 36 h post-surgery and analyzed using liquid chromatography-mass spectrometry. Principal component and partial least squares discriminant analyses were used to screen for differential metabolites and exclude exogenous metabolites at <i>p</i><0.05. Compounds were classified according to the HMDB (Human Metabolome Database), and subjected to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and VIP (variable importance in projection) analyses. Plasma metabolomics revealed that 86 metabolites were upregulated while 149 were downregulated, with (<i>Z</i>)-3-oxo-2-(2-pentenyl)-1-cyclopentylacetic acid, <i>trans</i>-cinnamic acid and cinnamoylglycine determined to be significant metabolites. Fifty-eight differential metabolites were upregulated in brain tissue and 53 were downregulated, with 2,3-dihydroflavon-3-ol, guanidinoacetic acid (GAA), <i>N</i>-acetyl-D-tryptophan, oxidized glutathione, 2-hydroxyquinoline, and <i>N</i>-acetyl-L-aspartate (NAA) identified as significant metabolites. Organic acids and derivatives, lipids and lipid-like molecules, organoheterocyclic compounds, and organic oxygen compounds were found to be common compound categories among the top five types of compound in both plasma and brain tissue. Common metabolic pathways in plasma and brain tissue include amino acid metabolism, digestive system, cancer overview, and lipid metabolism pathways, with the (<i>Z</i>)-3-oxo-2-(2-pentenyl)-1-cyclopentylacetic acid, GAA, oxidized glutathione, and NAA metabolites serving as potential biomarkers. This study provides a theoretical foundation for the early screening and development of clinical treatment strategies for IS.