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/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.
Conclusion
Our data suggest that alternatively activated macrophages may have some relationships
with angiogenesis of PDCN and hemorrhagic event of BAVM.
Key Words
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Article info
Publication history
Published online: December 24, 2015
Accepted:
November 22,
2015
Received in revised form:
September 29,
2015
Received:
August 10,
2015
Footnotes
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).
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.034
Copyright
© 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
