title: Alternatively Activated Macrophages Play an Important Role in Vascular Remodeling and Hemorrhaging in Patients with Brain Arteriovenous Malformation.
abstract: BACKGROUND
  Angiogenic and immunoactive lesions in brain arteriovenous malformation (BAVM) contribute to hemorrhagic events and the growth of BAVMs. However, the detailed mechanism is unclear. Our objective is to clarify the relationship between hemorrhagic events of BAVM and alternatively activated macrophages in the perinidal dilated capillary network (PDCN).
  
  
  METHODS
  We examined microsurgical specimens of BVMs (n = 29) and focused on the PDCN area. Ten autopsied brains without intracranial disease were the controls. We performed immunostaining of the inflammatory and endothelial cell markers, macrophage markers (CD163 and CD68), and vascular endothelial growth factor A (VEGF-A). We evaluated each cell's density and the vessel density in the PDCN and analyzed the relationship to hemorrhagic events of BAVM.
  
  
  RESULTS
  The PDCN was involved in all the resected arteriovenous malformations, and these vessels showed a high rate of CD105 expression (72.0 ± 10.64%), indicating newly proliferating vessels. Alternatively activated macrophages were found, with a high rate (85.6%) for all macrophages (controls, 56.6%). In the hemorrhagic cases, the cell density was significantly higher than that in the nonhemorrhagic cases and controls (hemorrhagic group, 290 ± 44 cells/mm(2); nonhemorrhagic group, 180 ± 59 cells/mm(2); and control, 19 ± 8 cells/mm(2)). The cell density of alternatively activated macrophages showed a positive correlation with the vessel density of the PDCN. Double immunostaining showed that VEGF-A was secreted by alternatively activated macrophages.
  
  
  CONCLUSIONS
  Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM.
authors.affiliation: Department of Neurosurgery, Kurume University of School of Medicine, Japan; Department of Pathology, Kurume University of School of Medicine, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Kurume University of School of Medicine, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugita
authors.affiliation: Department of Neurosurgery, Kurume University of School of Medicine, Japan; Department of Pathology, Kurume University of School of Medicine, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Department of Neurosurgery, Kurume University of School of Medicine, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Neurosurgery, Kurume University of School of Medicine, Japan.
authors.forename: Munetake
authors.initials: M
authors.lastname: Yoshitomi
authors.affiliation: Department of Pathology, Kurume University of School of Medicine, Japan.
authors.forename: Yoshizou
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Pathology, Kurume University of School of Medicine, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Neurosurgery, Kurume University of School of Medicine, Japan. Electronic address: mmorioka@med.kurume-u.ac.jp.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Morioka
authors.affiliation: Department of Pathology, Kurume University of School of Medicine, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002452:Cell Count; D002648:Child; D005260:Female; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000473:pathology* / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D066253:Vascular Remodeling / Q000502:physiology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D042461:Vascular Endothelial Growth Factor A
keywords: Arteriovenous malformation; VEGF; alternatively activated macrophage; perinidal dilated capillary network; vascular remodeling