摘要：SummaryCavernomas are multi-lumen and blood-filled vascular malformations which form in the brain and the spinal cord. They lead to hemorrhage, epileptic seizures, neurological deficits, and paresthesia. An effective medical treatment is still lacking, and the available murine models for cavernomas have several limitations for preclinical studies. These include disease phenotypes that differ from human diseases, such as restriction of the lesions to the cerebellum, and absence of acute hemorrhage. Additional limitations of current murine models include rapid development of lesions, which are lethal before the first month of age. Here, we have characterized a murine model that recapitulates features of the human disease: lesions develop after weaning throughout the entire CNS, including the spinal cord, and undergo acute hemorrhage. This provides a preclinical model to develop new drugs for treatment of acute hemorrhage in the brain and spinal cord, as an unmet medical emergency for patients with cavernomas.Graphical abstractDisplay OmittedHighlightsCcm3deletion in endothelial progenitors drives cavernoma formation in a mouse model•Mice develop acute hemorrhage and inflammation in brain and spinal cord•The spleen has increased vascular density and altered hemopoiesis•This model represents a useful tool for mechanistic studies and drug screeningVascular remodeling; Developmental neuroscience; Model organism
