Figure 4.

Endothelial Sox17 (SRY [sex-determining region Y]-box 17) deficiency exacerbates stroke outcome. A, Real-time quantitative polymerase chain reaction analysis of Sox17 expression in the ischemic forebrain of wild-type (wt) animals. Expression was determined in the ischemic brain hemisphere (ipsilesional) and in the nonischemic controlateral hemisphere (contralesional) at different days postischemia (dpi; n=3–8 mice per time point, mean±CI95%, **P≤0.01, compared with 0 dpi, 1-way ANOVA, and Bonferroni post hoc test). B, Tamoxifen was injected in 5-wk-old mice (3 injections every other day; black arrows). Two weeks later, mice underwent left middle cerebral artery occlusion (MCAO; green arrow) and analysed at the time points indicated in the specific panels. C, Modified Neurological Severity Score in wt and Sox17^iECKO mice (mean±SEM, *P≤0.05, 2-way ANOVA followed by Bonferroni post hoc test). D, Kaplan-Meier survival curve recorded in wt (n=11) and Sox17^iECKO (n=4) mice subjected to MCAO up to 4 dpi (n=11 wt and 4 Sox17^iECKO, **P≤0.01, Log-rank (Mantel-Cox) Test). E, Representative serial 3D reconstructions of the forebrains of a wt and a Sox17^iECKO mouse at 4 dpi. Yellow represents the ischemic lesion tissue. Red represents the healthy striatum. Blue represents the ventricles. Gray represents the contours of the hemispheres. F, Graphs representing the lesion volume (left) and the edema of the ipsilesional hemisphere (right; n=10 wt and 3 Sox17^iECKO, mean±SEM), (for lesion volume **P≤0.01, Mann-Whitney test), (for edema $P<0.05, 2-tailed t test and P=0.08, Mann-Whitney test). G, Confocal images of 1 representative cryosection from wt and Sox17^iECKO at 4 dpi stained for IgG (black). The presence of IgG leakage reveals loss of BBB integrity in Sox17^iECKO brains. Sections correspond to the bregma (0 mm). Scale bar: 1 mm. H, Quantification of IgG leakage from cryosections (n=5 wt and 3 Sox17^iECKO, mean±SEM, **P<0.01, Mann-Whitney).