• World Neurosurg · Nov 2021

    Involvement of neutrophil extracellular traps in cerebral arteriovenous malformations.

    • Kenji Shimada, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Shu Sogabe, Kazuhisa Miyake, Yoshiteru Tada, Keiko T Kitazato, Yasuhisa Kanematsu, and Yasushi Takagi.
    • Department of Neurosurgery, Tokushima University Hospital, Tokushima, Tokushima, Japan. Electronic address: s_kenji1032@yahoo.co.jp.
    • World Neurosurg. 2021 Nov 1; 155: e630-e636.

    BackgroundCerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs.MethodsWe analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients.ResultsExpression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus.ConclusionsOur results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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