The Ccm1iECKO mice and the Ccm2iECKO mice were generated by crossing the Cdh5-CreERT2;Ccm1fl/fl or Cdh5-CreERT2;Ccm2fl/fl mice with the Ccm1fl/fl or Ccm2fl/fl mice, respectively. To induce Ccm gene deletion, 50 μl of 4-HT (0.5 mg/ml; H7904, Sigma-Aldrich) was given intragastrically to neonatal pups at P1. Ponatinib [Selleck, 10 mg/kg made in 25 mM citrate buffer (pH 2.75)] was administrated to the neonatal CCM disease model via intragastric administration at either P6 or P11. Control animals were similarly injected with 4-HT and administered with vehicle [25 mM citrate buffer (pH 2.75)].

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