Metabolomic analysis reveals novel small molecule plasma markers of hyperacute ischemic stroke (S30.001)

Objective With metabolomics approach, we aimed to identify small molecule biomarkers in acute ischemic stroke (AIS) patients, which should facilitate our understanding of the pathology of stroke. Background As we conduct proteomic screen for blood biomarkers of AIS, we find many accompanying small molecule and peptides to be better markers for hyperacute ischemic injury. Since small metabolites can cross blood-brain barrier more easily than larger proteins, brain derived markers may potentially be better detected in blood as small molecules. Methods: Target small molecule (537) profiles of plasma from AIS patients (<6hr stroke onset) and control samples were studied by LC-MS approach followed by multivariate statistical analysis. Results: Principal components analysis (PCA) revealed that AIS patients and controls can be well distinguished by their metabolite composition. One-way ANOVA identified several metabolites differentially expressed in plasma between AIS patients and controls. Stroke patients had significantly reduced concentration of citrate (control: 7.39 ± 0.08; stroke: 7.17 ± 0.12; p-value = 0.0057), and elevated glutamate (Glu) (control: 4.28 ± 0.27; stroke: 5.12 ± 0.33; p-value = 0.006), and plasma lactate (PLA) (control: 5.40 ± 0.19; stroke: 5.69 ± 0.10, p-value = 0.0029). Other novel mediators were identified. Conclusions: Utilizing targeted metabolomics, we found increased Glu and PLA and decreased citrate level in AIS patients within 6 hours of stroke onset. Glu, an excitatory neurotransmitter, and PLA, a known apoptotic marker, are both found in CSF and peri-infarct zone of ischemic stroke. Citrate is not only important in energy metabolism (anaerobic glycolysis), but also binds blood calcium to prevent clot formation. Building on previous studies, this study is a first step to help understand early metabolic landscape of AIS and highlights the role of potential CSF contribution to peripheral metabolic contents. However, further study on source, time profile, and metabolomics-proteomics interaction, are needed and underway. Disclosure: Dr. Deng has nothing to disclose. Dr. Beecher has nothing to disclose. Dr. Burant has nothing to disclose. Dr. De Jong has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. Wickham has nothing to disclose. Dr. Elia has nothing to disclose. Dr. Feeney has nothing to disclose. Dr. McMullin has nothing to disclose. Dr. Buonanno has nothing to disclose. Dr. Eng H has nothing to disclose. Dr. Ning has nothing to disclose.