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(42%; 95% CI: 20‑67%) [Figure 1]. Hemosiderin positive DISCUSSION
cells were scattered mainly around the abnormal
vessels [Figure 1a]. Prussian blue positive staining We found in this study that T‑cells are the predominant
was detected in the areas that had hemosiderin lymphocytes in unruptured bAVMs. Few B‑lymphocytes
deposition [Figure 1d], suggesting the presence of and plasma cells were detected. Unlike macrophages,
previous micro‑hemorrhage. the number and location of T‑lymphocytes did not
correlate with hemosiderin, suggesting an independent
cell‑mediated immunological mechanism in bAVM
T-lymphocytes and macrophages were detected in pathogenesis.
unruptured brain arteriovenous malformations
To analyze whether the lymphocytes were present in Previously, immune cells were mostly analyzed in
unruptured bAVM and whether their location was ruptured [24] and irradiated [25] bAVMs. Our previous
associated with macrophages and iron deposition, study showed that adaptive immune cells were
we analyzed T‑ and B‑lymphocytes, plasma cells and rarely observed in unruptured bAVM. [13] We found
macrophages. We found that T‑lymphocyte was the in this study that many T‑lymphocytes were present
predominant type of lymphocytes present in unruptured in unruptured, previously untreated bAVMs. The
bAVM. Whereas the macrophages were scattered possible reason for the discrepancy is that we used a
mostly in the vessel walls and intervening stromal different immunohistochemical staining procedure in
regions [Figure 2], T‑lymphocytes were clustered on this study. Previously, we incubated sections in 0.3%
the luminal side of the endothelial surface, in the H O in methanol to quench the activity of endogenous
vascular wall, and in the tissue between abnormal peroxidase. However, lymphocyte surface markers have
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vessels [Figure 3]. Few B‑lymphocytes were detected; been shown to be sensitive to methanol/H O treatment.
they were mostly present in samples that had a large Treating sections with 0.3% H O in methanol can
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number of T‑lymphocytes, and were co‑localized reduce our ability to detect membrane markers on
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with the T‑lymphocytes [Figure 2]. In addition, a frozen sections, [26] and thus, we used 0.3% H O in
few plasma cells were identified in 5 samples, of PBS in this study. The case selection could also be
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which 4 had hemosiderin deposition (data not shown). responsible for the discrepancy.
No lymphocytes and macrophages were detected in
STA [Figure 2].
Humoral immunity has been reported to play an
important role in cerebral cavernous malformation,
Compared to the specimens that had no hemosiderin which might be due to chronic deposition of iron and
deposition, hemosiderin‑positive specimens blood degradation products. [22,27,28] Consistent with this
tended to have more macrophages (478 ± 174 vs. view, we found that plasma cells were present mainly in
666 ± 313 cells/mm ; P = 0.11). The T‑cell specimens that had hemosiderin deposition. However,
2
numbers were similar in hemosiderin‑positive we cannot draw any conclusion regarding adaptive
and hemosiderin‑negative samples (147 ± 108 vs. immune responses to the presence of iron from our
157 ± 139 cells/mm ; P = 0.88) [Figure 4]. small descriptive study.
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a b c

d e f
Figure 1: Hemosiderin deposition in unruptured brain arteriovenous malformations. H and E (a‑c) and prussian blue staining (d‑f) on the adjacent sections. (b) and
(c) are enlarged pictures of the regions in squares (b) and (c) in (a) showing hemosiderin‑positive areas. Insert in (b) shows two hemosiderin‑laden macrophages.
(d) Prussian blue staining of an adjacent section of (a). (e) and (f) are enlarged images of the regions in squares (e) and (f) in (d). Scale bars for a and d: 500 μm;
for b, c, e and f: 50 μm

Neuroimmunol Neuroinflammation | Volume 1 | Issue 3 | December 2014 149