Fig. 5

A Schematic representation of the experimental in vivo study. Animal ischemic model was induced by the local injection of thrombin in the middle cerebral artery (MCA). Treatments were injected through the vein 30 min after ischemia induction. Vehicle was used as control group. rtPAi (1 mg/kg as bolus and infusion), rtPA (1 mg/kg), rtPA-FITC (1 mg/kg), CSMs, CSM@rtPA (1 mg/kg as bolus) and CSM@rtPA/L (1 mg/kg as bolus) was administered as bolus. Infarct volumes and hemorrhages were evaluated at 24 h after ischemia by magnetic resonance imaging (MRI). B Ischemic lesion (white brain region) determined by T2-weighted at 24 h after the treatment administration in the experimental groups. Furthermore, the presence of hemorrhages was studied using the T2*-weighted images. C Analysis of the infarct volume at 24 h after the treatment administration. Dotted lines represent the median of the vehicle group. Dataare represented as mean ± SEM (n = 8 per treatment group). Statistical analysis was assessed by the on-way ANOVA followed by post-hoc Tukey’s test comparing all the groups against each other (*P < 0.05; **P < 0.01). D Analysis of hemorrhagic transformations evaluated by MRI T2*-weighted images. Dotted lines represent the median of the vehicle group. Dataare represented as mean ± SEM (n = 8 per treatment group). Statistical analysis was assessed by Kruskal–Wallis test followed by Dunn’s test comparing all the groups against each other. E Schematic representation of the inflammatory response study in ischemic mice. Treatments (vehicle and CSM@rtPA (1 mg/kg)) were administered 30 min after ischemia. Blood samples were extracted before and 6 h, 24 h, 3 and 7 days after the treatments to analyze F IL-6 and G TNF-α. Dotted lines represented the normal values of both inflammatory markers. These data represent mean ± SEM (n = 5 per group of treatment). Statistical analysis was assessed by Kruskal–Wallis test followed by Dunn’s multiple test compared with the corresponding basal timepoint (**P < 0.01; ***P < 0.001)