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Original Article

Distinctive distribution of lymphocytes in

unruptured and previously untreated brain

arteriovenous malformation

Yi Guo , Tarik Tihan , Helen Kim , Christopher Hess , Michael T. Lawton , William L. Young 1,4,5 ,
3
4
1
1,6
2
Yuan-Li Zhao , Hua Su 1
7
1 Department of Anaesthesia and Perioperative Care, Center for Cerebrovascular Research, San Francisco, CA 94110, USA.
2 Department of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
3 Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94110, USA.
4 Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94110, USA.
5 Department of Neurology, University of California, San Francisco, San Francisco, CA 94110, USA.
6 Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding 071000, Hebei, China.
7 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 410011, China.
ABSTRA CT

Aim: To test the hypothesis that lymphocyte infiltration in brain arteriovenous malformation (bAVM) is not associated with iron
deposition (indicator of micro‑hemorrhage). Methods: Sections of unruptured, previously untreated bAVM specimens (n = 19) were
stained immunohistochemically for T‑lymphocytes (CD3 ), B‑lymphocytes (CD20 ), plasma cells (CD138 ) and macrophages (CD68 ).
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Iron deposition was assessed by hematoxylin and eosin and Prussian blue stains. Superficial temporal arteries (STA) were used as
control. Results: Both T‑lymphocytes and macrophages were present in unruptured, previously untreated bAVM specimens, whereas
few B cells and plasma cells were detected. Iron deposition was detected in 8 specimens (42%; 95% confidence intervals = 20‑67%).
The samples with iron deposition tended to have more macrophages than those without (666 ± 313 vs. 478 ± 174 cells/mm ; P = 0.11).
2
T‑cells were clustered on the luminal side of the endothelial surface, on the vessel‑wall, and in the perivascular regions. There was
no correlation between T‑lymphocyte load and iron deposition (P = 0.88). No macrophages and lymphocytes were detected in STA
controls. Conclusion: T‑lymphocytes were present in bAVM specimens. Unlike macrophages, the load and location of T‑lymphocytes
were not associated with iron deposition, suggesting the possibility of an independent cell‑mediated immunological mechanism in
bAVM pathogenesis.
Key words: B‑lymphocyte, human brain arteriovenous malformation, inflammatory cells, micro‑hemorrhage, T‑lymphocyte

INTRODUCTION in the pathogenesis of bAVMs; [12] a confluence of these
factors has been proposed in a “response‑to‑injury”
Human brain arteriovenous malformations (bAVMs) paradigm. [5]
are tangles of abnormal vessels between arteries and
veins and lack of capillary bed. Brain AVM is the Evidence indicating the involvement of inflammation
most common cause of hemorrhagic stroke in young in bAVM pathogenesis includes neutrophil and
adults and children. [1‑3] Commonly assumed to be macrophage infiltration, and increased expression
congenital, postnatal formation may be more prevalent of various inflammatory signals, such as matrix
than previously thought, [4‑6] and the etiology of bAVMs metalloproteinase‑9, interleukin‑6, myeloperoxidase
still remains unclear. Genetic factors, [7,8] aberrant and adhesion molecules. [13‑18] About half of bAVMs
vasculogenesis, [9‑11] and inflammation may all play roles cases present with an intracranial hemorrhage (ICH),
which itself can induce inflammation. However,
Access this article online even in unruptured and untreated AVMs, substantial
Quick Response Code: infiltration of inflammatory cells has been detected
Website: in the vascular wall and intervening stroma. [13]
www.nnjournal.net
Magnetic resonance imaging has detected hemosiderin
DOI: deposition in unruptured bAVMs, [19,20] consistent
10.4103/2347-8659.143674 with episodes of clinically silent intralesional
micro‑hemorrhage.

Corresponding Author: Dr. Hua Su, Department of Anesthesia and Perioperative Care, University of California, San Francisco,
1001 Potrero Avenue, Box 1363, San Francisco, CA 94110. USA. E‑mail: hua.su@ucsf.edu

Neuroimmunol Neuroinflammation | Volume 1 | Issue 3 | December 2014 147