The image consists of six main panels labeled A through F. Panel A displays micro C T images of mouse brains harvested on post-operative day 21, comparing K r i t 1 f l slash f l; i P i k 3 c a H 1047 R mice treated with vehicle and those treated with Rebastinib. Panel B shows microscopic images through the cranial window, visual images, and micro C T renders of two Rebastinib-treated mice that developed significant C C M lesions, along with H and E and Prussian Blue staining. Panel C presents similar images for a Rebastinib-treated mouse that showed no typical C C M pathology. Panel D is a study flowchart outlining inclusion and exclusion criteria. Panel E includes microscopic and visual images of vehicle-treated mice showing large lesion formation. Panel F contains serial microscopic images through the cranial windows showing C C M growth in either vehicle- or Rebastinib-treated mouse brains from post-operative day 11 to 28.
Oral rebastinib treatment prevents de novo CCM formation but does not arrest the progression of existing lesions in the adult mice. (A) microCT images of all study subjects, including 9 Krit1fl/fl; iPik3caH1047R mice treated with vehicle and 13 Krit1fl/fl; iPik3caH1047R mice treated with rebastinib. Mouse brains were harvested on POD 21. Two pairs of representative microCT renders from this complete cohort are presented in Fig. 6 C with the corresponding brain specimens to demonstrate the effects of rebastinib treatment in lesion burden. (B and C) Representative microscopic images through the cranial windows (top left panels), visual images (top center panels), and microCT renders (top right panels), paired with H&E and Prussian blue staining (bottom panels) of (B) two rebastinib-treated Krit1fl/fl; iPik3caH1047R mice that developed significant CCM lesions by POD 21 and (C) one rebastinib-treated Krit1fl/fl; iPik3caH1047R mouse that showed no typical CCM pathology on POD 21. (D) Study flowchart outlining inclusion and exclusion criteria. (E) Representative microscopic images through the cranial windows (left panels) and visual images (right panels) of two vehicle-treated mice showing large lesion formation through cranial windows prior to study termination. (F) Serial of microscopic images through the cranial windows showing CCM growth in either vehicle- or rebastinib-treated mouse brains from POD 11 to POD 28. Two sets of representative microscopic images from this complete cohort are presented in Fig. 6 G to demonstrate the effects of rebastinib treatment in lesion burden. Scale bar: 1 mm.