Figure 3.
N-Acetyl-Cysteine induces recanalization after acute thrombosis in chronically hyperglycemic animals without risk of HT. (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 after stroke with saline (STZ) or rtPA (10mg/kg; Actilyse, 10% bolus, 90% perfusion during 40 minutes; STZ-rtPA group), NAC (400 mg/kg, slow bolus during 60 seconds; STZ-NAC group) or a combination of NAC and rtPA (STZ-NAC-rtPA group). 40.20 mm3 for STZ group (n = 14); 40.43 mm3 for STZ-rtPA group (n = 14); 26.92 mm3 for STZ-NAC group (n = 14); 21.59 mm3 for STZ-NAC-rtPA group (n = 14). Ordinary one-way ANOVA (P < .001); Tukey test for multiple comparisons (∗P < .05; ∗∗∗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-NAC and STZ-NAC-rtPA groups. (D) Percentage of angiographic scores 24 hours after MCAo assessed by FLASH_TOF_2D imaging (7T MRI) in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 13-14 per group). No recanalization = complete occlusion (orange); partial recanalization = incomplete filling of the distal bed (light green); complete recanalization = complete filling of the distal bed (dark green). Kruskal-Wallis test (P < .01); Dunn’s test for multiple comparisons (∗P < .05, ∗∗P < .01). (E) Proportion of HT per groups 24 hours after MCAo assessed by T2∗-weighted imaging (deoxyhemoglobin; 7T MRI) in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 14 per group). 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) on day before and on day 1, day 3, and day 7 after MCAo in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 14 per group). Data were assessed in grams. 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). (G) Quantification of the global strength deficit measured by grip-test of forepaws before and on days 1, 3, and 7 after MCAo in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 14 per group). 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).

N-Acetyl-Cysteine induces recanalization after acute thrombosis in chronically hyperglycemic animals without risk of HT. (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 after stroke with saline (STZ) or rtPA (10mg/kg; Actilyse, 10% bolus, 90% perfusion during 40 minutes; STZ-rtPA group), NAC (400 mg/kg, slow bolus during 60 seconds; STZ-NAC group) or a combination of NAC and rtPA (STZ-NAC-rtPA group). 40.20 mm3 for STZ group (n = 14); 40.43 mm3 for STZ-rtPA group (n = 14); 26.92 mm3 for STZ-NAC group (n = 14); 21.59 mm3 for STZ-NAC-rtPA group (n = 14). Ordinary one-way ANOVA (P < .001); Tukey test for multiple comparisons (∗P < .05; ∗∗∗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-NAC and STZ-NAC-rtPA groups. (D) Percentage of angiographic scores 24 hours after MCAo assessed by FLASH_TOF_2D imaging (7T MRI) in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 13-14 per group). No recanalization = complete occlusion (orange); partial recanalization = incomplete filling of the distal bed (light green); complete recanalization = complete filling of the distal bed (dark green). Kruskal-Wallis test (P < .01); Dunn’s test for multiple comparisons (∗P < .05, ∗∗P < .01). (E) Proportion of HT per groups 24 hours after MCAo assessed by T2∗-weighted imaging (deoxyhemoglobin; 7T MRI) in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 14 per group). 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) on day before and on day 1, day 3, and day 7 after MCAo in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 14 per group). Data were assessed in grams. 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). (G) Quantification of the global strength deficit measured by grip-test of forepaws before and on days 1, 3, and 7 after MCAo in STZ, STZ-rtPA, STZ-NAC and STZ-NAC-rtPA groups (n = 14 per group). 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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