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Concomitant coiling reduces metalloproteinase levels in flow diverter-treated aneurysms but anti-inflammatory treatment has no effect.

Abstract：

BACKGROUND AND PURPOSE:Flow diverters (FD) can cause rare but devastating delayed aneurysm ruptures in which matrix metalloproteinases (MMPs) have been potentially implicated. Concomitant coiling or anti-inflammatory medications have been proposed to prevent the risk of delayed ruptures. The aim of this study was to evaluate concomitant coiling and ciclosporin in regulating the expression of MMPs in FD-treated aneurysms. MATERIALS AND METHODS:Elastase-induced aneurysms were created in 20 rabbits. Aneurysms were treated with (1) FD alone; (2) FD with concomitant coiling; (3) FD+ ciclosporin; or (4) left untreated as controls. At sacrifice, MMP levels were analyzed by zymography. Kruskal-Wallis one-way non-parametric ANOVA was performed for each enzyme. If significant results were observed for the Kruskal-Wallis test, pairwise group comparisons were performed using Dunn's test with Bonferroni multiple-testing correction. RESULTS:Significant differences were observed among groups for pro-MMP9 (p=0.0337). Pairwise comparison demonstrated higher levels of pro-MMP9 with concomitant coiling compared with untreated aneurysms (p=0.012), with higher though not significantly different levels of pro-MMP9 in FD with concomitant coiling versus FD alone. While not statistically significant, trends were noted regarding differences in active-MMP9 across groups, with a lower level of active-MMP9 with concomitant coiling compared with the other FD groups. No significant differences were observed for pro- or active-MMP2 across groups, or for FD + ciclosporin compared with FD alone. CONCLUSIONS:FD implantation increases the level of pro-MMP9 expression in aneurysms. Provocative trends regarding modulation of active-MMP9 expression with concomitant coiling suggest the need for larger confirmatory preclinical studies. Anti-inflammatory treatment with ciclosporin appears to have a minimal biological effect. TRIAL REGISTRATION NUMBER:R01NS076491.

journal_name

J Neurointerv Surg

journal_title

Journal of neurointerventional surgery

authors

Thielen E,McClure M,Rouchaud A,Ding YH,Dai D,Schroeder D,Cebral J,Kallmes DF,Kadirvel R

doi

10.1136/neurintsurg-2015-012207

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

307-310

issue

eissn

1759-8478

issn

1759-8486

pii

neurintsurg-2015-012207

journal_volume

pub_type

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Concomitant coiling reduces metalloproteinase levels in flow diverter-treated aneurysms but anti-inflammatory treatment has no effect.