{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:55:00Z","timestamp":1782899700036,"version":"3.54.5"},"reference-count":81,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS126415"],"award-info":[{"award-number":["R01NS126415"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013568","name":"The Aneurysm and AVM foundation","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100013568","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS135153"],"award-info":[{"award-number":["R01NS135153"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"AVM Research Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Dipaolo and Theaker families","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,23]]},"abstract":"<jats:p>\n                    Mutation of KRAS in endothelial cells (KRAS-ECs) leads to intracerebral hemorrhage (ICH) in brain arteriovenous malformation (bAVM), resulting in severe disabilities or even death. However, it is unclear what causes this hemorrhagic conversion of bAVMs. Here, using a locally established, clinically relevant sporadic bAVM mouse model, created by overexpressing mutant KRAS (KRAS\n                    <jats:sup>G12V<\/jats:sup>\n                    ) in brain ECs, we demonstrate that KRAS-ECs act as trigger for activation of microglia (MG) and infiltration of macrophages (M\u03d5). Using a 3-dimensional immunostaining approach with cleared human and mouse bAVM tissues, we demonstrate an abundance of MG\/M\u03d5 around the bAVM nidus. The presence of MG\/M\u03d5 was correlated to the blood-brain barrier leakage in bAVM areas. Time-lapsed intravital imaging in\n                    <jats:italic>Cx3cr1-gfp;Ccr2-rfp<\/jats:italic>\n                    reporter mice demonstrated the dynamic activation of MG and infiltration of M\u03d5 toward mutant KRAS\n                    <jats:sup>G12V<\/jats:sup>\n                    \u2013modified dysplastic vessels. Importantly, a time-course analysis showed that these activated MG and infiltrated M\u03d5 are present around the bAVMs prior to hemorrhagic conversion, and controlled depletion of MG\/M\u03d5 reduced ICH incidence in bAVMs. Inhibition of MG\/M\u03d5 with long-term minocycline treatment attenuated the incidence of ICHs around bAVMs. Our study indicates that MG\/M\u03d5 are involved in destabilization of KRAS\n                    <jats:sup>G12V<\/jats:sup>\n                    -induced bAVM, leading to hemorrhagic conversion\/ICH. Thus, modulation of MG\/M\u03d5 may reduce ICH risk in patients with bAVM.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.195638","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T15:32:27Z","timestamp":1771255947000},"source":"Crossref","is-referenced-by-count":2,"title":["Endothelial oncogenic KRAS mutation drives the dynamics of microglia and macrophages in brain arteriovenous malformation"],"prefix":"10.1172","volume":"11","author":[{"given":"Hyejin","family":"Park","sequence":"first","affiliation":[{"name":"Vivian L. Smith Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Vivian L. Smith Department of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridger H.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Vivian L. 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