Background:
As we conduct proteomic screening for blood biomarkers of acute ischemic injury, we find many accompanying small molecules and peptides to be better markers for hyperacute ischemic injury. Since these small metabolites can cross the blood-brain barrier more easily than larger proteins, brain-derived markers may potentially be better detected in blood as small molecules. Here we used a targeted approach to identify small molecule biomarkers in acute ischemic stroke patients.
Methods:
Target small molecule (537) profiles of acute ischemic stroke (<6hr post stroke onset) and control blood were analysed by LC-MS followed by multivariate analysis.
Results:
Principal component analysis (PCA) shows stroke and controls can be very well distinguished by their composite metabolic profiles (Figure 1A). One-way ANOVA identified metabolites differentially expressed in plasma between stroke vs controls. Stroke patients had significantly reduced relative concentration (expressed as peak area) of citrate (control-c: 7.39 ± 0.08; stroke-s: 7.17 ± 0.12; p=0.0057), and elevated glutamate (Glu) (c: 4.28 ± 0.27; s: 5.12 ± 0.33; p=0.006), and plasma lactate (PLA) (c: 5.40 ± 0.19; s: 5.69 ± 0.10, p=0.0029) (Figure 1B-D). Other novel mediators were also identified (not shown due to space).
Conclusions:
Utilizing targeted metabolomic analysis, we found increased Glu and PLA and decreased citrate levels in acute ischemic stroke patients within 6 hours of stroke onset. Glu, an excitatory neurotransmitter, and PLA, a known apoptotic marker, are both found in CSF and in the peri-infarct ischemic zone. Citrate is not only important in energy metabolism (TCA cycle), but also binds calcium to prevent clot formation. Building on previous studies, this proof-of-concept analysis helps to understand the early metabolic landscape of hyperacute ischemic stroke in peripheral plasma. Further studies of sources, time profiles, and metabolomic-proteomic interactions are needed.
Comparative Genomic and Metabolomic Analysis of
Termitomyces
Species Provides Insights into the Terpenome of the Fungal Cultivar and the Characteristic Odor of the Fungus Garden of
Macrotermes natalensis
Termites
