Itaconate modulated brain redox metabolism in a cerebral ischemia-reperfusion model. A) Experimental overview of a mouse animal model of acute cerebral ischemia. Mice were infused with NaCl (vehicle, blue), or itaconate (15 mg/kg/min, red) for 30 min prior to ligation. 60 min after ligation, reperfusion was initiated and the mice were infused again for 30 min. B) Plasma itaconate levels 2 and 24 h after reperfusion. C) Plasma metabolite levels 24 h after reperfusion in vehicle compared to itaconate-treated group relative to baseline. D) Total glutathione levels in brain tissue 24 h after reperfusion. E) Reduced glutathione (GSH) levels in brain tissue 24 h after reperfusion. F) Oxidized glutathione (GSSG) levels in brain tissue 24 h after reperfusion. G) GSH (reduced)/GSSG (oxidized) glutathione levels in brain tissue 24 h after reperfusion. H) Reduction potential (NADH/NAD ratio) indicating mitochondrial oxidative phosphorylation 2 h after reperfusion relative to baseline. I) Reactive oxygen/nitrogen species (ROS/RNS) in brain tissue 2 h after reperfusion. Data are represented as box (25th to 75th percentile with median line) and whiskers (min. to max. values) (B, D-G, and I) or means ± s.e.m. (C and H). Experiments were performed with n = number of male mice aged 9 weeks. Two-way ANOVA (B with n = 2 for vehicle and n = 5 for itaconate; H, n = 5) or one-way ANOVA (D-G and I, n = 5) with *P < 0.05, **P < 0.01, and ***P < 0.001.