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ID 116871
Title Alternative
INVOLVEMENT OF NETS IN CEREBRAL AVM
Author
Miyamoto, Takeshi Tokushima University
Kitazato, Keiko T. Tokushima University
Keywords
Cerebral arteriovenous malformation
Citrullinated histone-H3
Neutrophil extracellular traps
Content Type
Journal Article
Description
BACKGROUND: Cerebral 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.
METHODS: We 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.
RESULTS: Expression 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.
CONCLUSIONS: Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs.
Journal Title
World Neurosurgery
ISSN
18788750
NCID
AA12469471
AA12725298
Publisher
Elsevier
Volume
155
Start Page
e630
End Page
e636
Published Date
2021-08-31
Rights
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital
Medical Sciences