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).
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.
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/mm2; nonhemorrhagic group, 180 ± 59 cells/mm2; and control, 19 ± 8 cells/mm2). 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.
Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM.
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Published online: December 24, 2015
Accepted: November 22, 2015
Received in revised form: September 29, 2015
Received: August 10, 2015
Grant support: This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Science and Culture of Japan (15K10322).
© 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.