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Updated: Jun 30, 2026

Imaging Vital and Non-vital Brain Pericytes in Brain Slices following Subarachnoid Hemorrhage
Published on: August 18, 2023
Evidence of inflammatory cell involvement in brain arteriovenous malformations
Yongmei Chen1, Wei Zhu, Andrew W Bollen
1Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, USA.
Objective:
Brain arteriovenous malformations (AVM) have high matrix metalloproteinase-9, interleukin-6, and myeloperoxidase (MPO) expression, and polymorphic variations in inflammatory genes are associated with an increased risk of hemorrhage. In this study, we characterized the presence of inflammatory cells in AVM lesional tissue specimens.
Methods:
Immunohistochemistry was used to identify and localize neutrophils (MPO as marker), macrophages/microglia (CD68 as marker), T lymphocytes (CD3 as marker), and B lymphocytes (CD20 as marker). Endothelial cell (EC) marker CD31 was used as an index to assess vascular mass (EC mass). Surgical specimens from 20 unruptured, nonembolized AVMs were examined; seven cortical samples from temporal lobectomy were used as controls. Positive signals for inflammatory cell markers were counted and analyzed by normalizing to the area of the tissue section and the amount of endothelial cells (cells/mm/EC mass pixels). Levels of MPO and matrix metalloproteinase 9 were determined by enzyme-linked immunosorbent assay.
Results:
Neutrophils and macrophages are all frequently identified in the vascular wall of AVM tissue. In contrast, T and B lymphocytes are rarely observed in AVM tissue. AVM tissue displayed more neutrophil and macrophage/microglia markers than epilepsy control tissue (MPO: 434 +/- 333 versus 5 +/- 4, P = 0.0001; CD68: 454 +/- 404 versus 4 +/- 2, P = 0.0001; cells/mm/EC mass pixels). In ex vivo studies, neutrophil quantity, MPO, and matrix metalloproteinase-9 levels were all colinear (R = 0.98-0.99).
Conclusion:
Our study demonstrates that inflammatory cells are present in AVM tissue. Taken together with previous genetic and cytokine studies, these data are consistent with a novel view that inflammation is associated with AVM disease progression and rupture.
Insights
Inflammatory cells, including neutrophils and macrophages, are present in brain arteriovenous malformation (AVM) tissue. This finding supports the role of inflammation in AVM disease progression and rupture risk.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Brain arteriovenous malformations (AVMs) are associated with high expression of inflammatory markers like matrix metalloproteinase-9 and myeloperoxidase (MPO).
- Genetic variations in inflammatory genes correlate with an increased risk of AVM hemorrhage.
Purpose of the Study:
- To investigate the presence and types of inflammatory cells within brain arteriovenous malformation (AVM) lesional tissue.
- To correlate inflammatory cell presence with AVM characteristics and potential rupture risk.
Main Methods:
- Immunohistochemistry was employed to identify neutrophils (MPO+), macrophages/microglia (CD68+), T lymphocytes (CD3+), and B lymphocytes (CD20+) in AVM specimens.
- Endothelial cell (EC) mass was assessed using CD31 staining to normalize inflammatory cell counts.
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify MPO and matrix metalloproteinase-9 levels.
Main Results:
- Neutrophils and macrophages were frequently detected in the vascular walls of AVM tissues, unlike T and B lymphocytes which were rare.
- AVM tissues showed significantly higher neutrophil and macrophage/microglia marker expression compared to epilepsy control tissues.
- Ex vivo analysis revealed a strong linear correlation between neutrophil quantity, MPO levels, and matrix metalloproteinase-9.
Conclusions:
- The study confirms the presence of inflammatory cells within brain AVM tissue.
- These findings, combined with prior research, suggest a significant role for inflammation in the progression and potential rupture of AVMs.
- Inflammation may represent a novel therapeutic target for managing AVM disease.
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