Abstract 76: Transient Depletion of Microglia Reduces the Severity of Brain Arteriovenous Malformation in a Mouse Model

Background and purpose: Accumulation of macrophages and microglia is evidenced in the lesions of human and mouse brain arteriovenous malformations (bAVMs) with or without hemorrhage, suggesting that these cells play an active role in bAVM pathogenesis. We hypothesize that transient depletion of microglia reduces bAVM severity. Methods: Brain AVM was induced in adult mice that have activin-like kinase 1 (Alk1, an AVM causative gene) gene exons 4-6 floxed by co-injection of an adenoviral vectors expressing Cre-recombinase and an adeno-associated viral vectors expressing vascular endothelial growth factor into the basal ganglia. Brain microglia were depleted transiently by administration of an inhibitor of colony stimulating factor receptor (CSF1R inhibitor, 180 mg/kg/day of body weight) through chow for 7 days starting 1- (when angiogenesis occurred) or 8-weeks (when bAVMs had formed) after model induction. Brain AVM severity was analyzed through quantification of abnormal vessels, macrophage/microglia and ...