An Effective and Simple Way to Establish Elastase-Induced Middle Carotid Artery Fusiform Aneurysms in Rabbits

Abstract

Objective. Elastase-induced aneurysms in rabbits have been proposed as a preclinical tool for device development, but there is still much deficiency in those aneurismal models. So we need to explore the efficient and convenient animal models for the investigation of intracranial aneurysms. Then, we compared and analyzed three methods of elastase-induced carotid artery aneurysms in rabbits and aimed to find a simple, effective, and reproducible method for creating elastase-induced aneurysms. Methods. 42 standard feeding male adult Japanese white rabbits (3.05±0.65 kg) were randomly divided into 3 groups and treated with elastase ablation to create common carotid artery (RCCA) aneurysm models: Group A (root-RCCA medication group, n=12), Group B (mid-RCCA medication group, n=18), and Group C (ligated RCCA+medication group, n=12). For Group A, the origin of the RCCA was blocked by two temporary aneurysm clips, and the resulting 2 cm cavity was infused with elastase for 20 min, then the clip was removed and the RCCA was not ligated. For Group B, the middle part of RCCA was treated the same way as Group A and the RCCA was not ligated. For Group C, the middle part of RCCA was treated as Group B, but the distal RCCA was ligated. After the aneurysm models were created for 3 weeks, prior to sacrificing the animals, color Doppler ultrasound and angiography were performed for blood flow measurements inside the aneurysms. Histological analysis (such as SMA-α, CD31, CD34, CD68, collagen IV, and Ki67) and the other relevant indexes were compared between the ideal model’s aneurysmal tissues and the human intracranial aneurysm’s tissues to confirm whether we have successfully established elastase-induced aneurysm models. Results. Compared with human intracranial aneurysm specimens by the color Doppler ultrasound, angiography, and changes in the inner diameter of arteries, all three methods have successfully established the elastase-induced aneurysm models. Histology showed that biological responses were similar to both human cerebral aneurysms and previously published elastase-induced rabbit aneurysm models. Group A and Group B had the same morphology, but Group A had a higher mortality rate than Group B. Group B and Group C had different morphology. The aneurysm of Group C was more similar to human cerebral aneurysms but had a higher mortality rate than Group B. Group B was confirmed not only as an alternative method but also as a more safe and effective method for creating elastase-induced aneurysm models. Conclusion. Through analysis and comparison, the Group B is proven to be the simplest, reproducible, and most effective modeling method. The aneurysm model established by Group B can be used for basic research related to aneurysm mechanism. We have provided a new and effective method for basic research on aneurysm.

Imaging of intracranial aneurysms in animals: a systematic review of modalities

“…In 1993, Hashimoto [ 31 ] used this modality to measure blood flow velocity in a rabbit venous pouch IA model. Since then, this technique has been used in a number of IA studies to study blood flow velocity in cerebral arteries or within the IA and to check IA patency over time or after treatments [ 41 , 42 , 44 , 91 , 154 , 176 , 178 ].…”

“…[ 173 ] 2019 X Surgical Dogs Saccular X X X Rajabzadeh-Oghaz H. [ 174 ] 2019 X Endogenous Mice Saccular X Wanderer S. [ 175 ] 2020 X Surgical Rabbits Saccular X X Lyu Y. [ 176 ] 2020 X Surgical Rabbits Fusiform X X Fries F. [ 177 ] 2020 X Surgical Rabbits Saccular X …”

Uncovering of Key Pathways and miRNAs for Intracranial Aneurysm Based on Weighted Gene Co-Expression Network Analysis

“…The copy number of hsa-miR-3907 was higher in autosomal dominant polycystic kidney disease patients with hypertension than in autosomal dominant polycystic kidney disease patients without hypertension [40]. Previous studies have shown that the CD34 molecule (CD34) is an important regulator of chronic inflammatory vascular disease, and its levels are abnormal in aneurysms [41]. In the present study, MFAP4 and CD34 were the target DEmRNAs of hsa-miR-4793-3p and hsa-miR-3907, respectively.…”

Imaging Modalities for Intracranial Aneurysm: More Than Meets the Eye

“…To the best of our knowledge, only 2 studies managed to follow aneurysmal remodeling in mice over 3 months using really high-field MRI (9,4T) ( 100 , 101 ). Regarding IA's hemodynamics, Doppler ultrasound imaging can be used to measure blood flow velocity in rabbit models of internal carotid aneurysm ( 99 , 102 , 103 ).…”