The use of bioactive and hydrophilic coils may further promote endothelial cell proliferation

No time-dependent comparison of the histologic changes has been described. In this study we observed the proliferation of endothelial cells in a sidewall-type aneurysm model in the first 4 weeks after embolization. There are many histopathological reports of small animal aneurysm models, such as mouse, rat and rabbit, however, in these animals, the vessel structure and coverage of endothelial cells are different to those seen in humans. The small animal models can only be used to study small aneurysms and it is difficult to use devices such as microcatheters and guidewires designed for humans. Moreover, the type of microglia, the inflammatory response, and the structure of blood vessels differ fundamentally from humans as a consequence of differences between the human and rodent immune systems. Surgical construction of experimental aneurysms in large animals was first described in the dog in the mid 1950s and, more recently, in swine. Their large blood vessels make surgical construction, pathophysiological investigation, and subsequent endovascular or surgical treatment of aneurysms considerably easier than in small animals. Swine have been proposed as a particularly useful model because of similarities in the swine and human coagulation systems. In addition, large animal models have been extensively used for preclinical testing of endovascular devices, and similarly good outcomes can be achieved in large animals and humans �C reflected in the findings of this study. Previous studies have described Coptisine-chloride endothelialization using macroscopically, using H&E, elastic and trichrome staining, Masson trichrome and reticulin staining, scanning electron microscopy and TEM. At the neck of the aneurysm, the fresh thrombus was progressively replaced by fibrous tissue, growing inwards from the margins. Fibrous obliteration of the neck occurred more rapidly than resolution of the Epimedoside-A intraluminal blood clot and was present, together with endothelial overgrowth, as early as 14 days after coil embolization. Our study showed a similar pattern of endothelial cell growth. We detected vWF- and PCNA-positive cells in the proliferating tissue, suggesting that they were proliferating endothelial cells. Moreover, the time-dependent increase in the number of PECAM-1 positive cells, the presence of only cytoplasm, a nucleus, and a nucleolus at 1 week after coil embolization, and the observation of mitochondria, rough endoplasmic reticulum, ribosomes, and tight junctions at 2 and 4 weeks after coil embolization, suggest that the proliferating cells are maturing. Here, we present our findings from the sidewall-type aneurysm model, but we have also developed a terminal-type aneurysm model, which displays long-term patency. Because the hemodynamic characteristics of sidewall- and terminal-type aneurysms differ, we also plan to study endothelial cell proliferation in the terminal type aneurysm model. Moreover, future studies could also examine the influence of bioactive and hydrophilic coils, balloons, stents, and antiplatelet drugs on embolism and the proliferation of an endothelial lining in both models. We detected an endothelium-lined layer of connective tissue between the aneurysm and parent artery after embolization.

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