Glunomab coupled with a thrombolytic agent improves stroke outcome and protects against HT in chronically hyperglycemic animals. (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 mice treated with saline (STZ group), rtPA (10mg/kg; Actilyse, 10% bolus, 90% perfusion over 40 minutes; and STZ-rtPA group), Glunomab (300 μg, 100% bolus; STZ-Gluno group), a combination of Glunomab and rtPA (STZ-Gluno-rtPA group), and a combination of Glunomab and NAC (400 mg/kg, slow bolus) on hyperglycemic mice. Individual values, means, and SEM are plotted; 28.80 mm³ for STZ group (n = 16); 27.66 mm³ for STZ-rtPA group (n = 15); 20.14 mm³ for STZ-Gluno group (n = 15); 15.64 mm³ for STZ-Gluno-rtPA group (n = 16); and 14.88 mm³ for STZ-NAC-Gluno group (n = 15). Ordinary 1-way ANOVA (P < .001); Tukey multiple comparisons (∗∗P < .01 and ∗∗∗P < .001). (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, STZ-Gluno, STZ-Gluno-rtPA, and STZ-NAC-Gluno groups. (D) Percentage of angiographic scores, 24 hours after MCAo assessed by FLASH_TOF_2D imaging (7T MRI) in STZ (n = 15), STZ-rtPA (n = 14), STZ-Gluno (n = 15), STZ-Gluno-rtPA (n = 15), and STZ-Gluno-NAC (n = 14) 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 < .05); Dunns test for multiple comparisons (∗P < .01 and ∗∗P < .01). (E) Proportion of HT per groups, 24 hours after MCAo assessed by T2∗-weighted imaging (deoxyhemoglobin; 7T MRI) in STZ (n = 16), STZ-rtPA (n = 15), STZ-Gluno (n = 15), STZ-Gluno-rtPA (n = 16), and STZ-Gluno-NAC (n = 15) groups. Fisher exact tests between groups (∗P < .05). (F) Quantification of the specific left paw–strength deficit measured by grip-test ratio (strength of left/right paws) of STZ (n = 16), STZ-rtPA (n = 15), STZ-Gluno (n = 15), STZ-Gluno-rtPA (n = 16), and STZ-Gluno-NAC (n = 15) groups, 1 day before, and on day 1, day 3, and day 7 after MCAo. Data were assessed in grams. Results are represented in mean ± SEM; 2-way ANOVA: time effect <0.0001 and group effect <0.01; Tukey test for multiple comparison (∗P < .05 between groups at each time; $P < .5 vs baseline for each group: impact of Stroke; #P < .5 vs day 1 for each group: recovery). (G) Quantification of the global strength deficit measured by grip-test of forepaws of STZ (n = 16), STZ-rtPA (n = 15), STZ-Gluno (n = 15), STZ-Gluno-rtPA (n = 16), and STZ-Gluno-NAC (n = 15) groups 1 day before and on day 1, day 3, and day 7 after MCAo. Data were assessed in grams and converted in percentage normalized for each animal with the corresponding baseline value (before MCAo). Results are represented in mean ± SEM; 2-way ANOVA: time factor <0.0001; Tukey test for multiple comparison (∗P < .05 between groups at each time; $P < .5 vs baseline for each group: impact of Stroke; #P < .5 vs day 1 for each group: recovery).