Involvement of neutrophils in machineries underlying the rupture of intracranial aneurysms in rats

Scientific Reports
Mika KushamaeTomohiro Aoki

Abstract

Subarachnoid hemorrhage due to rupture of an intracranial aneurysm has a quite poor prognosis after the onset of symptoms, despite the modern technical advances. Thus, the mechanisms underlying the rupture of lesions should be clarified. To this end, we obtained gene expression profile data and identified the neutrophil-related enriched terms in rupture-prone lesions using Gene Ontology analysis. Next, to validate the role of neutrophils in the rupture of lesions, granulocyte-colony stimulating factor (G-CSF) was administered to a rat model, in which more than half of induced lesions spontaneously ruptured, leading to subarachnoid hemorrhage. As a result, G-CSF treatment not only increased the number of infiltrating neutrophils, but also significantly facilitated the rupture of lesions. To clarify the mechanisms of how neutrophils facilitate this rupture, we used HL-60 cell line and found an enhanced collagenolytic activity, corresponding to matrix metalloproteinase 9 (MMP9), upon inflammatory stimuli. The immunohistochemical analyses revealed the accumulation of neutrophils around the site of rupture and the production of MMP9 from these cells in situ. Consistently, the collagenolytic activity of MMP9 could be detected in the ...Continue Reading

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Citations

Oct 13, 2021·Cellular and Molecular Neurobiology·Shusheng WuLongfei Du
Nov 4, 2021·Stroke; a Journal of Cerebral Circulation·Shuhei KawabataHaruhiko Kishima

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Datasets Mentioned

BETA
GSE161044

Methods Mentioned

BETA
RNA-Seq
ELISA
SMA
zymography

Software Mentioned

CLC genomics workbench system
CLC genomics workbench
PHASES
DESeq
RNA
Seq
edgeR

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