Rupture of brain aneurysms is associated with high fatality and morbidity rates. Through remodeling of the collagen matrix, many aneurysms can remain unruptured for decades, despite an enlarging and evolving geometry. Our objective was to explore this adaptive remodeling for the first time in an elastase induced aneurysm model in rabbits. Saccular aneurysms were created in 22 New Zealand white rabbits and remodeling was assessed in tissue harvested 2, 4, 8 and 12 weeks after creation. The intramural principal stress ratio doubled after aneurysm creation due to increased longitudinal loads, triggering a remodeling response. A distinct wall layer with multi-directional collagen fibers developed between the media and adventitia as early as 2 weeks, and in all cases by 4 weeks with an average thickness of 50.6 ± 14.3 μm. Collagen fibers in this layer were multi-directional (AI = 0.56 ± 0.15) with low tortuosity (1.08 ± 0.02) compared with adjacent circumferentially aligned medial fibers (AI = 0.78 ± 0.12) and highly tortuous adventitial fibers (1.22 ± 0.03). A second phase of remodeling replaced circumferentially aligned fibers in the inner media with longitudinal fibers. A structurally motivated constitutive model with both remodeling modes was introduced along with methodology for determining material parameters from mechanical testing and multiphoton imaging. A new mechanism was identified by which aneurysm walls can rapidly adapt to changes in load, ensuring the structural integrity of the aneurysm until a slower process of medial reorganization occurs. The rabbit model can be used to evaluate therapies to increase aneurysm wall stability.

中文翻译：

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弹性蛋白酶诱导的兔动脉瘤的适应性重塑


脑动脉瘤破裂与高死亡率和发病率相关。通过胶原基质的重塑，许多动脉瘤可以在几十年内保持不破裂，尽管其几何形状不断扩大和演变。我们的目标是首次在弹性蛋白酶诱导的兔子动脉瘤模型中探索这种适应性重塑。在 22 只新西兰白兔中制作囊状动脉瘤，并在制作后 2、4、8 和 12 周收集的组织中评估重塑情况。由于纵向载荷增加，动脉瘤形成后，壁内主应力比加倍，引发重塑反应。早在 2 周内，中膜和外膜之间就形成了具有多向胶原纤维的独特壁层，在所有情况下均在 4 周内形成，平均厚度为 50.6 ± 14.3 μm。与相邻的周向排列的内侧纤维（AI = 0.78 ± 0.12）和高度弯曲的外膜纤维（1.22 ± 0.03）相比，该层中的胶原纤维是多向的（AI = 0.56 ± 0.15），具有低弯曲度（1.08 ± 0.02）。重塑的第二阶段用纵向纤维取代了内部介质中的周向排列的纤维。引入了具有两种重塑模式的结构驱动本构模型以及通过机械测试和多光子成像确定材料参数的方法。确定了一种新的机制，通过该机制，动脉瘤壁可以快速适应负荷的变化，确保动脉瘤的结构完整性，直到发生较慢的内侧重组过程。兔模型可用于评估增加动脉瘤壁稳定性的疗法。