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- W1497373323 abstract "Background and Purpose: Monocytes are present in human brain arteriovenous malformation (bAVM), but their roles and origin are not clear. Endoglin (Eng, a bAVM causative gene) mutation extends CD68+ cell retention in the mouse stroke brain. Using 2 mouse bAVM models, we tested the hypothesis that CD68+ cells in bAVM are mostly active microglia, which cause unresolved inflammation and lesion progression. Methods: In Model 1, using Rosa-CreER;Eng-floxed mice, AVM was induced through global Eng deletion, and brain focal angiogenesis stimulated by an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF). In Model 2, using CCR2RFP/+/CX3CR1GFP/+;Alk1 (another bAVM causative gene) floxed mice, AVM was induced through focal Alk1 deletion, and angiogenesis by intra-brain injection of Ad-Cre and AAV-VEGF. The RFP+ and GFP+ and CD68+ cells in the bAVM were quantified. Results: The mice in both models had bAVM 8 weeks after model induction. The bAVM lesions had more CD68+ cells than the normal angiogenic region of wild-type (WT) mouse brain (Model 1 vs. WT: 562±182/mm2 vs. 353±86, P=0.049; and Model 2 vs. WT: 890±289 vs. 549±72, P=0.058). Most (95%) CD68+ cells in Model 2 were GFP+ microglia. Model 2 mice also had more RFP+ bone marrow (BM)-derived macrophages than WT controls (P=0.065), suggesting that unmutated BM-derived macrophages also participate in bAVM pathogenesis. A similar number of CD68+ cells was detected in the brain angiogenic foci in Model 1 mice (P=0.29) 2 weeks after model induction. Conclusions: These data indicate a consistent infiltration of active microglia in bAVM that causes unresolved inflammation, which then promotes abnormal angiogenesis and lesion progression. Unmutated BM-derived microphages also participate in this process." @default.
- W1497373323 created "2016-06-24" @default.
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- W1497373323 date "2015-02-01" @default.
- W1497373323 modified "2023-10-16" @default.
- W1497373323 title "Abstract 191: Persistent Infiltration of Active Microglia in Brain Arteriovenous Malformation Causes Unresolved Inflammation and Lesion Progression" @default.
- W1497373323 doi "https://doi.org/10.1161/str.46.suppl_1.191" @default.
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