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Original research
Concomitant coiling reduces metalloproteinase levels in flow diverter-treated aneurysms but anti-inflammatory treatment has no effect
  1. Evan Thielen1,
  2. Megan McClure1,
  3. Aymeric Rouchaud1,
  4. Yong-Hong Ding1,
  5. Daying Dai1,
  6. Dana Schroeder1,
  7. Juan Cebral2,
  8. David F Kallmes1,3,
  9. Ramanathan Kadirvel1
  1. 1Applied Neuroradiology Laboratory, Mayo Clinic, Rochester, Minnesota, USA
  2. 2George Mason University, Bioengineering, Fairfax, Virginia, USA
  3. 3Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Aymeric Rouchaud, Neuroradiology Research Laboratory, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA; aymeric.rouchaud{at}


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

  • Coil
  • Aneurysm
  • Flow Diverter
  • Inflammation

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  • Contributors All authors participated in drafting the article and revising it critically for important intellectual content. All authors made substantial contributions to conception and design, acquisition of the data, and analysis and interpretation of the data. All authors provided final approval of the version to be published.

  • Funding This work was supported by NIH grant R01NS076491

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The authors are willing to share spreadsheets from their data extraction on request.