Bare, Bio-Active and Hydrogel-Coated Coils for Endovascular Treatment of Experimentally Induced Aneurysms

Summary Pre-clinical studies are important in helping practitioners and device developers improve techniques and tools for endovascular treatment of intracranial aneurysms. Thus, an understanding of the major animal models used in such studies is important. The New Zealand rabbit elastase induced arterial aneurysm of the common carotid artery is one of the most commonly used models in testing the safety and efficacy of new endovascular devices. In this review we discuss 1) various techniques used to create the aneurysm, 2) complications of aneurysm creation, 3) natural history of the arterial aneurysm, 4) histopathologic and hemodynamic features of the aneurysm 5) devices tested using this model and 6) weaknesses of the model. We demonstrate how pre-clinical studies using this model are applied in treatment of intracranial aneurysms in humans. The model has a similar hemodynamic, morphological and histologic characteristics to human aneurysms and demonstrates similar healing responses to coiling as human aneurysms. Despite these strengths however, the model does have many weaknesses including the fact that the model does not emulate the complex inflammatory processes affecting growing and ruptured aneurysms. Furthermore the model’s extracranial location affects its ability to be used in preclinical safety assessments of new devices. We conclude that the rabbit elastase model has characteristics that make it a simple and effective model for preclinical studies on the endovascular treatment of intracranial aneurysms however further work is needed to develop aneurysm models that simulate the histopathologic and morphologic characteristics of growing and ruptured aneurysms.

Section: Device Testingsupporting

confidence: 80%

From bench to bedside: utility of the rabbit elastase aneurysm model in preclinical studies of intracranial aneurysm treatment

Brinjikji

Ding

Kallmes

et al. 2015

“…Insertion of many coils is similar to achieving a high VER. The VER has recently been reported to be associated with aneurysmal recanalization 21 22. Many procedures and devices have been considered to increase the VER.…”

Section: Discussionmentioning

confidence: 99%

Optimal first coil selection to avoid aneurysmal recanalization in endovascular intracranial aneurysmal coiling

Neki

Kohyama

Otsuka

et al. 2017

“…In addition, the shape of the coil and configuration might also affect the endothelialization process. Reinges et al 8 compared endothelialization of aneurysms embolized with bare, bioactive and hydrogel-coated coils in the rabbit model and suggested that a smooth and dense surface over the aneurysm neck is important for endothelial cells to bridge the aneurysm neck. The lack of neointimal coverage at the aneurysm neck leads to coil compaction and subsequently, recanalization of the aneurysm 22.…”

Section: Discussionmentioning

confidence: 99%

Characterizing patterns of endothelialization following coil embolization: a whole-mount, dual immunostaining approach

Dai

Ding

Rezek

et al. 2015

Background The extent, rate, and source of endothelialization following coil embolization of saccular aneurysms remains poorly understood. We performed a whole tissue mount, dual immunohistochemical analysis of experimental aneurysms in order to characterize the state of endothelialization over time following platinum coil embolization. Method and material Elastase-induced rabbit aneurysms were created and treated with bare platinum coils. Samples were harvested at 4 and 8 weeks (n=6 for each). En face whole tissue mounts staining using antibodies for CD31 and α-smooth muscle actin to identify endothelial cells and smooth muscle cells, respectively. Sytox green stain was employed to demonstrate nuclear morphology for identification of inflammatory cells. Extent of endothelialization was measured in relation to the aneurysm neck-parent artery interface. Results At 4 weeks following coil embolization, very localized membranous tissue and neoendothelial cells were detected on the coil loops immediately adjacent to the parent artery-neck interface, but the remainder of the coil loops remained devoid of endothelial cells. At 8 weeks neo-endothelial cells were more confluent over the coils than at 4 weeks, and extended up to 900μm from the parent artery-neck interface. However, the surfaces of the coils farther than this region harbored no endothelial cells. Scattered inflammatory cells including neutrophils, and monocytes were observed on the coil surface at the neck center area, where the coil surface was bare grossly at the 4 and 8 weeks follow up. Conclusion Platinum coil embolization supports gradual but limited endothelialization, where endothelial cells migrate directly from the adjacent parent artery.