Thrombomodulin is expressed in a heterogeneous manner in Ccm3-iECKO mice. (A) Kinetic expression of thrombomodulin at P6, P7, and P8 in the cerebellum (cb) shows that thrombomodulin expression decreased in wild-type mice (red line) but remained high in Ccm3-iEKO mice (blue line). Thrombomodulin was significantly higher in Ccm3-iEKO at P7 (P = .0190). and P8 (P = .0043) when compared with wild-type mice. (B) Representative images of the cerebellum of wild-type (upper panel) and Ccm3-iECKO (lower panel) P8 mice stained with isolectin (green) and thrombomodulin (red). A merged image is shown in the right panel. (C) Images of the heterogeneous expression of erythrocytes (green) and thrombomodulin (red) show how (i) lesions filled with erythrocytes have a lower expression of thrombomodulin, whereas lesions that are hallowed (ii) and (iii) have a high expression of thrombomodulin. (D) Images showing the heterogeneous expression of VWF (green) and thrombomodulin (red) showing how some regions express high levels of vascular and extracellular VWF with thrombomodulin (dashed box, split channels to the right), and other vessels express low levels of VWF (asterisks). White arrows highlight secreted VWF, and yellow arrows highlight thrombomodulin/VWF colocalization. In panel A, the mean of n = 12 mice in each group are shown. Bars indicate the standard deviation in each group. A Mann-Whitney U test was used to compare wild-type mice with Ccm3-iECKO mice; the corresponding P values are indicated on each graph.