4.2 Article

Aneurysm Organization Effects of Gellan Sulfate Core Platinum Coil with Tenascin-C in a Simulated Clinical Setting and the Possible Mechanism

Journal

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
Volume 25, Issue 4, Pages 771-780

Publisher

ELSEVIER
DOI: 10.1016/j.jstrokecerebrovasdis.2015.12.010

Keywords

Tenascin-C; gellan sulfate; transforming growth factor-beta; elastase-induced rabbit aneurysms; coil embolization

Funding

  1. Mie Society for the Promotion of Medical Research
  2. New Energy and Industrial Technology Development Organization [05A04018a]
  3. Japan Society for the Promotion of Science [21390410, 24592122]
  4. Grants-in-Aid for Scientific Research [24592122] Funding Source: KAKEN

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Background: This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting. Methods: Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm-occlusion status was evaluated angiographically and histologically at 2 weeks post coiling. As each rabbit coiled aneurysm provided only 2-3 tissue slices due to technical limitations and prevented immunohistochemical evaluations, a PC, GSCC, or GSCC-TNC was randomly implanted in a rat blind-ended model (n = 3, respectively) and the organization effects were immunohistochemically evaluated for expressions of tenascin-C (TNC), transforming growth factor-beta (TGF-beta), and matrix metalloproteinase-9 (MMP-9) 2 weeks later. Results: Coil handling was similar among the 3 kinds of coils. GSCCs showed a significantly higher ratio of organized area to the aneurysmal cavity than PCs, but GSCC-TNCs had the greatest organization-promoting effects on aneurysms (the ratio of organized area/aneurysmal luminal area: PC, 17.9 +/- 7.1%; GSCC, 54.2 +/- 18.3%; GSCC-TNC, 82.5 +/- 5.8%). GSCC-TNCs had intense immunoreactivities for TNC, TGF-beta, and MMP-9 in the organized thrombosis and tunica media. GSCCs also showed intense immunoreactivities for TNC, TGF-beta, and MMP-9, although the extent was less than GSCC-TNCs. The immunoreactivities were hardly found in unorganized thrombus and the tunica media of aneurysm wall in the PC group. Conclusions: This study first showed that GSCC-TNCs promote intra-aneurysmal clot organization in simulated clinical settings using rabbits possibly through the TGF-beta and MMP-9 upregulation.

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