• Tomohiro Aoki, Hiroharu Kataoka, Masaki Nishimura, Ryota Ishibashi, Ryuichi Morishita, and Susumu Miyamoto.
• Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto City, Kyoto, Japan.
• Neurosurgery. 2012 Jun 1;70(6):1534-43; discussion 1543.

BackgroundDespite a high mortality and morbidity of subarachnoid hemorrhage due to an intracranial aneurysm (IA), there is no effective medical treatment to prevent the rupture of IAs. Recent studies have revealed the involvement of the transactivation of proinflammatory genes by nuclear factor-κB (NF-κB) and Ets-1 in the pathogenesis of IA formation and enlargement.ObjectiveTo examine the regressive effect of chimeric decoy oligodeoxynucleotides (ODNs), which simultaneously inhibit NF-κB and Ets-1, on IA development in the rat model.MethodsOne month after IA induction, rats were treated with NF-κB decoy ODNs or chimeric decoy ODNs. Size, media thickness, macrophage infiltration, and collagen biosynthesis in IA walls were analyzed in both groups.ResultsThe treatment with chimeric decoy ODNs decreased IA size and thickened IA walls of preexisting IAs induced in the rat model, although the treatment with NF-κB decoy ODNs failed to regress preexisting IAs. Chimeric decoy ODN-treated rats exhibited decreased expression of monocyte chemotactic protein-1 and macrophage infiltration in IA walls. In addition, decreased collagen biosynthesis in IA walls was ameliorated in the chimeric decoy ODN-treated group.ConclusionThe results suggest the possibility of a minimally invasive molecular therapy targeting the inhibition of NF-κB and ets-1 for IAs in humans.

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