Fig. 5: Impaired clot resolution in CCM is improved with Cl-amidine treatment.
a, Representative images of acute (left) and chronic/organized (right) clots from the cerebellum of Ccm3-iECKO vehicle mice stained with DAPI (blue), TER-119 (green) and podocalyxin (white). b–d, Representative image of organized clots from the cerebellum of Ccm3-iECKO vehicle mice with increased ICAM-1 expression (red) (b), infiltrated with CD45+ cells (green) (c) and with increased expression of vimentin (green) and α-SMA (magenta) (d). e, Representative image showing endothelization of organized clots in the cerebellum of Ccm3-iECKO vehicle mice stained with DAPI (blue), TER-119 (green) and podocalyxin (white). Insets with red line highlight the magnifications to the right, with red arrow highlighting new vessels. f,g, Quantification of number of mice with organized clot (f) and organized clot area (g) in the cerebellum of Ccm3-iECKO Ccm3-iECKO vehicle-treated (n = 13) and Cl-amidine-treated (10 mg kg−1 d−1; n = 8) mice. Each data point represents one biological replicate; the bar indicates the median of each group; and the error bars represent the IQR. Statistical significance was determined using a Mann–Whitney U-test (two-tailed). h, Representative images of patients with familial CCM (fCCM) showing acute (black box) and organized (yellow box) clots. Samples were stained for CD34 (top panel), hematoxylin and eosin (middle panel) and Fraser–Lendrum stain (bottom panel). The stains were repeated independently in all samples (n = 3) with similar results. i, Representative images of acute (black box) and organized (yellow box) clots in sporadic CCM (sCCM) patient biopsy stained with DAPI (blue), vWF (green), α-SMA (red) and fibrin (white). Insets with white lines highlight the magnifications below. The stains were repeated independently in all samples (n = 4) with similar results. j, Representative images stained with DAPI (blue) and α-SMA (red) showing different clot stages from acute (white box; a) to intermediate (yellow box; b) and organized (yellow box; c) clots. Insets highlight the magnifications to the right. a: lesion without α-SMA deposition—acute clot; b: lesion with moderate α-SMA deposition—intermediate clot; c: lesion with intense α-SMA deposition—organized clot. The stains were repeated independently in all samples (n = 4) with similar results. cb, cerebellum.
