A murine model of cerebral cavernous malformations with acute hemorrhage

Cavernomas are multi-lumen and blood-filled vascular malformations which form in the brain and the spinal cord. They lead to hemorrhage, epileptic seizures, neurological defi zits, and paresthesia. An effective medical treatment is still lacking, and the available murine models for cavernomas have several limitations for predinical 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.

Automated summary

Cavernomas are vascular malformations that form in the brain and spinal cord, causing symptoms such as hemorrhage and epileptic seizures. Current murine models have limitations in reproducing the characteristics of the human disease. A newly characterized murine model recapitulates features of human cavernomas, providing a preclinical model for developing drugs to treat acute hemorrhage.