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Mol. Life Sci."],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an\u00a0endothelial cell-specific ablation of the <jats:italic>Ccm3<\/jats:italic> gene (<jats:italic>Ccm3<\/jats:italic><jats:sup><jats:italic>iECKO<\/jats:italic><\/jats:sup>), we show that  endothelial cells from <jats:italic>Ccm3<\/jats:italic><jats:sup><jats:italic>iECKO<\/jats:italic><\/jats:sup> mice have an\u00a0increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the <jats:italic>Ccm3<\/jats:italic><jats:sup><jats:italic>iECKO<\/jats:italic><\/jats:sup> mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the\u00a0formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of <jats:italic>Ccm3<\/jats:italic><jats:sup><jats:italic>iECKO<\/jats:italic><\/jats:sup> mice. Degradation of NETs by DNase I treatment improved the\u00a0vascular barrier. The deposition of NETs in the cavernomas \u00a0of patients with CCM confirms the clinical relevance of NETs in CCM.<\/jats:p>","DOI":"10.1007\/s00018-022-04224-2","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T10:03:03Z","timestamp":1648202583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Inflammation and neutrophil extracellular traps in cerebral cavernous malformation"],"prefix":"10.1007","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1570-7813","authenticated-orcid":false,"given":"Anthony C. 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