Effects of ticagrelor in a mouse model of ischemic stroke

Figures

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  Figure 1. Effects of ticagrelor on platelet aggregation and infarct volume 22 hours after reperfusion. (A) Experimental protocol for the measurement of platelet aggregation and infarct volume. (B) Adenosine diphosphate-induced platelet aggregation after administration of ticagrelor. Data are expressed as means ± standard errors of the mean (SEMs). N = 3 or 4 per group; **P < 0.01 vs. vehicle; Student’s t-test. (C) Representative images of triphenyltetrazolium chloride-stained coronal slices 22 hours after reperfusion. (D) Quantitative measurements of infarct volume 22 hours after reperfusion. Data are expressed as means ± SEMs. N = 10 to 12 per group; *P < 0.05 vs. vehicle; Student’s t-test.

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  Figure 2. The effects of ticagrelor on neurological deficits. (A) Neurological deficits 22 hours after reperfusion measured using Garcia score. (B) Neurological deficits 22 hours after reperfusion measured using the grid walk test. N = 10 to 12 per group; *P < 0.05 vs. vehicle; Wilcoxon signed-rank test. (C) The experimental protocol used to measure the neurological score. (D) The results of Garcia scores within 7 days after ischemia. N = 10 to 12 per group; **P < 0.01 vs. vehicle; Wilcoxon signed-rank test.

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  Figure 3. The effects of ticagrelor on cerebral blood flow (CBF), as measured using laser speckle Doppler. (A) The experimental protocol used for the CBF measurements. (B) Quantitative data of CBF within 24 hours after reperfusion. Data are expressed as means ± standard errors of the mean. N = 7 to 9 per group; *P < 0.05 vs. vehicle; Student’s t-test. (C) Representative images of CBF. The oval area in the image obtained from ticagrelor-treated mice before middle cerebral artery occlusion indicates the region of interest.

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  Figure 4. The effects of ticagrelor on phosphorylation of endothelial nitric oxide synthase (eNOS) after reperfusion. (A) The protocol used for western blotting. The effects of ticagrelor on the phosphorylation of endothelial nitric oxide synthase 2 hours (B), 8 hours (C), and 22 hours (D) after reperfusion. Data are expressed as means ± standard errors of the mean. N = 5 or 6 per group; #P < 0.05, ##P < 0.01 vs. control, *P < 0.05 vs. vehicle; Student’s t-test. The cropped blots are used in this Figure and the full-length blots are presented in Supplementary Figure S1.

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  Figure 5. The effects of ticagrelor on the phosphorylation of extracellular signal-regulated kinase 1/2 two hours after reperfusion. Data are expressed as means ± standard errors of the mean. N = 5 or 6 per group; **P < 0.01 vs. control, #P < 0.05 vs. vehicle; Student’s t-test. The cropped blots are used in this Figure and the full-length blots are presented in Supplementary Figure S2.

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  Figure 6. Effects of ticagrelor in sham-operated mice. (A) The experimental protocol used for western blotting. The effects of ticagrelor on the phosphorylation of endothelial nitric oxide synthase (B) and extracellular signal-regulated kinase 1/2 (C) in sham-operated mice. Data are expressed as means ± standard errors of the mean. N = 5 per group. The cropped blots are used in this Figure and the full-length blots are presented in Supplementary Figure S3.

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  Figure 7. In vitro analysis using oxygen-glucose deprivation (OGD) stress in human brain microvessel endothelial cells (HBMVECs). (A) The experimental protocol used to assess the effects of ticagrelor against OGD stress in HBMVECs. (B) Cell viability measured using cell counting kit 8 two hours after reoxygenation. Data are expressed as means ± standard errors of the mean (SEMs). N = 12 per group; #P < 0.05 vs. vehicle; Dunnett’s test. The effects of ticagrelor on the phosphorylation of endothelial nitric oxide synthase (C) and extracellular signal-regulated kinase 1/2 (D) 2 hours after reoxygenation. Data are expressed as means ± SEMs. n = 4 per group; ##P < 0.01 vs. vehicle; Dunnett’s test. The cropped blots are used in this Figure and the full-length blots are presented in Supplementary Figure S4.