Chronic hyperglycemia induces rtPA resistance and increases HT independently of the therapeutic window. (A) Schematic representation of the experimental protocol. (B) Quantification of ischemic lesion volume, 24 hours after MCAo assessed by T2-weighted imaging (7T MRI) in hyperglycemic mice treated with saline (STZ group) or rtPA (10 mg/kg; Actilyse, 10% bolus, 90% perfusion during 40 minutes), in early 20 minutes after MCAo (STZ-rtPA-early) or in late 4 hours after MCAo (STZ-rtPA-late). Individual values, means, and SEM are plotted; 34.45 mm³ for STZ group (n = 10); 37.01 mm³ for STZ-rtPA-early group (n = 5); and 33.98 mm³ for STZ-rtPA-late group (n = 5). Ordinary 1-way ANOVA (P = .14). (C) Representative T2-weighted 7T MRI brain images (left) and representation of the lesion distribution around bregma (right) 24 hours after MCAo in STZ, STZ-rtPA-early and STZ-rtPA-late groups. (D) Percentage of angiographic scores, 24 hours after MCAo assessed by FLASH_TOF_2D imaging (7T MRI) in STZ (n = 10), STZ-rtPA-early (n = 5), and STZ-rtPA-late (n = 5) groups. No recanalization = complete occlusion (orange); partial recanalization = incomplete filling of the distal bed (light green); and complete recanalization = complete filling of the distal bed (dark green). Kruskal-Wallis test (P = .16). (E) Proportion of HT per group, 24 hours after MCAo assessed by T2∗-weighted imaging (deoxyhemoglobin; 7T MRI) in STZ (n = 10), STZ-rtPA-early (n = 5), and STZ-rtPA-late (n = 5) groups. Fisher exact tests between groups (P > .05).