Figure 1.
Chronic hyperglycemia induces rtPA resistance and increases HT in a mouse model of thromboembolic stroke. (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 saline or rtPA treated (10 mg/kg; Actilyse, 10% bolus, 90% perfusion during 40 minutes) on nonhyperglycemic mice (Ctrl) or on hyperglycemic mice (STZ). Individual values, means, and standard error of the mean (SEM) are plotted; 23.38 mm3 for Ctrl group (n = 13); 12.88 mm3 for Ctrl-rtPA group (n = 13); 36 mm3 for STZ group (n = 12); 39.58 mm3 for STZ-rtPA group (n = 12). Ordinary 1-way analysis of variance (ANOVA) (P < .01); Tukey test for multiple comparisons (∗∗P < .01; ∗∗∗∗P < .0001). (C) Representative T2-weighted 7T MRI brain images (left) and representation of the lesion distribution around bregma (right), 24 hours after MCAo in Ctrl, Ctrl-rtPA, STZ, and STZ-rtPA groups. (D) Percentage of angiographic scores 24 hours after MCAo assessed by FLASH TOF 2D imaging (7T MRI) in Ctrl (n = 13), Ctrl-rtPA (n = 12), STZ (n = 12), and STZ-rtPA (n = 12) 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 < .01); Dunns test for multiple comparisons (∗∗P < .01). (E) Proportion of HT per groups, 24 hours after MCAo assessed by T2∗-weighted imaging (deoxyhemoglobin; 7T MRI) in Ctrl (n = 13), Ctrl-rtPA (n = 13), STZ (n = 12), and STZ-rtPA (n = 12) 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 Ctrl, Ctrl-rtPA, STZ, and STZ-rtPA groups (n = 12) before MCAo and on days 1, 3, and 7 after MCAo. Data were assessed in grams. Results are represented in mean ± SEM; 2-way ANOVA: time × group effect = 0.0211; 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 Ctrl, Ctrl-rtPA, STZ, and STZ-rtPA groups (n = 12) before and on days 1, 3, and 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, and group factor <0.001; 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).

Chronic hyperglycemia induces rtPA resistance and increases HT in a mouse model of thromboembolic stroke. (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 saline or rtPA treated (10 mg/kg; Actilyse, 10% bolus, 90% perfusion during 40 minutes) on nonhyperglycemic mice (Ctrl) or on hyperglycemic mice (STZ). Individual values, means, and standard error of the mean (SEM) are plotted; 23.38 mm3 for Ctrl group (n = 13); 12.88 mm3 for Ctrl-rtPA group (n = 13); 36 mm3 for STZ group (n = 12); 39.58 mm3 for STZ-rtPA group (n = 12). Ordinary 1-way analysis of variance (ANOVA) (P < .01); Tukey test for multiple comparisons (∗∗P < .01; ∗∗∗∗P < .0001). (C) Representative T2-weighted 7T MRI brain images (left) and representation of the lesion distribution around bregma (right), 24 hours after MCAo in Ctrl, Ctrl-rtPA, STZ, and STZ-rtPA groups. (D) Percentage of angiographic scores 24 hours after MCAo assessed by FLASH TOF 2D imaging (7T MRI) in Ctrl (n = 13), Ctrl-rtPA (n = 12), STZ (n = 12), and STZ-rtPA (n = 12) 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 < .01); Dunns test for multiple comparisons (∗∗P < .01). (E) Proportion of HT per groups, 24 hours after MCAo assessed by T2∗-weighted imaging (deoxyhemoglobin; 7T MRI) in Ctrl (n = 13), Ctrl-rtPA (n = 13), STZ (n = 12), and STZ-rtPA (n = 12) 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 Ctrl, Ctrl-rtPA, STZ, and STZ-rtPA groups (n = 12) before MCAo and on days 1, 3, and 7 after MCAo. Data were assessed in grams. Results are represented in mean ± SEM; 2-way ANOVA: time × group effect = 0.0211; 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 Ctrl, Ctrl-rtPA, STZ, and STZ-rtPA groups (n = 12) before and on days 1, 3, and 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, and group factor <0.001; 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).

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