Abstract 3187: Inflammatory Cell Infiltration Correlates with Hemosiderin Deposition (Intra-lesion Hemorrhage) in Surgical Excised Unruptured Human Brain Arteriovenous Malformations

Abstract

Background and Purpose: Human brain arteriovenous malformations (bAVM) are common cause of hemorrhagic stroke in young adults. Evidence of inflammation in bAVM pathogenesis includes neutrophil and macrophage infiltration, and increased expression of various inflammatory signals, such as matrix metalloproteinase-9, interleukin-6, myeloperoxidase and adhesion molecules. Hemosiderin deposition in unruptured bAVM has been detected by magnetic resonance imaging (MRI), consistent with episodes of clinically silent micro-hemorrhage. We hypothesized that the inflammatory cell (macrophage and lymphocyte) burden is positively correlated with the degree of hemosiderin deposition in the lesion. Methods: A total of 19 unruptured, non-embolized surgically-excised bAVM specimens were examined. Macrophages (CD68+), T-lymphocytes (CD3+), and B-lymphocytes (CD20+) were detected by immunohistochemical staining using specific antibodies and quantified using stereological microscopy. Hemosiderin deposition were detected on H&E stained sections and confirmed by Prussian blue staining. Prussian blue positive cells were quantified by NIH image J software. Three superficial temporal arteries (STA) were used as controls. Results: Both CD68+ cells (5-75×103/cm2) and CD3+ cells (0-34×103/cm2) were detected in bAVM samples. Few CD20+ cells were detected. The CD3+ cells were clustered on the lumen surface of endothelial cells, in the vascular wall and, in some cases, in the perivascular regions. In contrast, CD68 and hemosiderin staining was observed in a more diffuse pattern.. No CD68+, CD3+ and CD20+ cells were detected in STA. Hemosiderin deposition (Prussian blue positive) was present in 8/19 (42%) patients and was co-localized with CD68+ cells. Conclusions: In addition to CD68+ cells, the finding that T lymphocytes were prominently present in bAVM lesion raises the question of the relationship of cell-mediated immunological mechanisms to bAVM pathogenesis and/or clinical course. The causal link between cellular infiltration and extravasated blood remains indeterminate, the co-localization of CD68+ cells and micro-hemorrhage_cellular infiltration may represent novel risk factors for clinical AVM rupture risk.