Rabbit Model Of Aneurysm Research Articles

CD31 Mimetic Coating Enhances Flow Diverting Stent Integration into the Arterial Wall Promoting Aneurysm Healing

Beyond aneurysmal occlusion, metallic flow diverters (FDs) can induce an adverse endovascular reaction due to the foreignness of metal devices, hampering FD endothelialization across the aneurysm neck, and arterial healing of intracranial aneurysms. Here, we evaluated the potential benefits of an FD coating mimicking CD31, a coreceptor critically involved in endothelial function and endovascular homeostasis, on the endothelialization of FDs implanted in vivo. Nitinol FD (Silk Vista Baby) and flat disks were dip-coated with a CD31-mimetic peptide via an intermediate layer of polydopamine. Disks were used to assess the reaction of endothelial cells and blood elements in vitro. An aneurysm rabbit model was used to compare in vivo effects on the arterial wall of CD31-mimetic-coated (CD31-mimetic, n=6), polydopamine-coated (polydopamine, n=6), and uncoated FDs (bare, n=5) at 4 weeks post-FD implantation. In addition, long-term safety was assessed at 12 weeks. In vitro, CD31-mimetic coated disks displayed reduced adhesion of blood elements while favoring endothelial cell attachment and confluence, compared to bare and polydopamine disks. Strikingly, in vivo, the neoarterial wall formed over the CD31-mimetic-FD struts at the aneurysm neck was characteristic of an arterial tunica media, with continuous differentiated endothelium covering a significantly thicker layer of collagen and smooth muscle cells as compared to the controls. The rates of angiographic complete occlusion and covered branch arterial patency were similar in all 3 groups. CD31-mimetic coating favors the colonization of metallic endovascular devices with endothelial cells displaying a physiological phenotype while preventing the adhesion of platelets and leukocytes. These biological properties lead to a rapid and improved endothelialization of the neoarterial wall at the aneurysm neck. CD31-mimetic coating could therefore represent a valuable strategy for FD biocompatibility improvement and aneurysm healing.

Modified Intravascular Interventional Operation of Balloon-Bound Elastase Induction Method to Establish Rabbit Aneurysm Model Using Cardiovascular Angiography

Objective: In this paper, we establish a simple, efficient and stable rabbit aneurysm model using modified intravascular interventional operation of balloon-bound elastase induction method. Methods: We selected 20 healthy adult New Zealand white rabbits. An aortic aneurysm model of rabbit right common carotid artery was established by modified intravascular interventional balloon-binding elastase induction method using cardiovascular angiography. The cerebral angiography confirmed the model successfully after 4 weeks. Some animals were given paraffin-embedded H-E staining and elastic fiber staining after sacrifice. Angiography was performed for all experiments to build our models and to confirm our findings. Results: Two rabbits died during postoperative feeding, and the remaining 18 rabbits were cultured for 4 weeks and confirmed by angiography to make an aneurysm model. The success rate of aneurysm was 90%, the diameter of the tumor-bearing artery was 3.12±0.20, the short diameter of the tumor was 3.41±0.88, the long diameter of the tumor was 6.30±1.65, and the width of the neck was 3.49±0.80. HE pathology showed that the destruction of the elastic layer of the aneurysm disappeared, similar to the pathological changes of human aneurysms. Conclusions: The rabbit model of aneurysm was established by modified intravascular intervention combined with elastase induction based on angiography. It is similar to human aneurysm in morphology, histology and hemodynamics. The method is simple, the damage is small, the aneurysmal formation rate is high, and the performance is high. Stable and reliable, low production cost, it is an ideal animal model for the development of preclinical neurological interventional devices.

Multiphoton microscopy for pre-clinical evaluation of flow-diverter stents for treating aneurysms

BackgroundConventional histological analyses are the gold standard for the study of aneurysms and vascular pathologies in pre-clinical research. Over the past decade, in vivo and ex vivo imaging using multiphoton microscopy have emerged as powerful pre-clinical tools for detailed tissue analyses that can assess morphology, the extracellular matrix (ECM), cell density and vascularisation. Multiphoton microscopy allows for deeper tissue penetration with minor phototoxicity. ObjectiveThe present study aimed to demonstrate the current status of multimodality imaging, including multiphoton microscopy, for detailed analyses of neo-endothelialisation and ECM evolution after flow-diverter stent (FDS) treatment in an experimental rabbit model of aneurysms. MethodsMultiphoton microscopy tools for assessing autofluorescence and second harmonic generation (SHG) signals from biological tissues were used to evaluate the endovascular treatment of intracranial aneurysms in an animal model of aneurysms (pig, rabbit). Results from multiphoton microscopy were compared to those from standard histology, electronic and bright field microscopy. ConclusionsThe present study describes novel evaluation modes based on multiphoton microscopy for visualising tissue morphology (e.g., collagen, elastin, and cells) to qualify and quantify the extent of neo-intimal formation of covered arteries and device integration into the arterial wall using a rabbit model of intracranial aneurysms treated with FDS.

Stromal cell-derived factor 1α facilitates aneurysm remodeling in elastase-induced rabbit saccular aneurysm

AimsInflammation plays a crucial role in aneurysm wall remodeling, which could lead to the rupture of intracranial aneurysms. Stromal cell-derived factor 1α (SDF-1α), a vital inflammation cytokine, is also related to aneurysm pathogenesis. However, the characteristics of SDF-1α expression and its role in aneurysm remodeling remain largely unknown. In this study, we aimed to investigate the expression dynamics of SDF-1α and its correlation with aneurysm remodeling. MethodsSaccular aneurysms were induced by porcine pancreatic elastase in New Zealand White rabbits. Aneurysm size was measured by digital subtraction angiography. Endothelial-like cells on the aneurysm wall were assessed on postoperative days 1, 3, 7, 14, 21, and 30. SDF-1α levels in the aneurysmal wall and serum were examined at several follow-up time points. Adherent molecule expression was examined, and migration assays were performed in vitro. After SDF-1α stimulation, the mobilization of endothelial-lineage cells and its role in the reendothelialization of the aneurysm wall were investigated in a saccular aneurysm rabbit model. ResultsAfter the creation of saccular aneurysms in rabbits, the aneurysm sacs were filled with acute thrombosis within 3days, followed by a significant enlargement on day 14 and maturation on day 21. Serum SDF-1α levels increased in a bimodal fashion on day 1 and day 14, whereas SDF-1α expression in the aneurysm wall reached its maximum on day 14. VE-cadherin was up-regulated after SDF-1α stimulation and down-regulated by the SDF-1α ligand blocker AMD3100. Endothelial progenitor cell migration was enhanced by SDF-1α and blocked by AMD3100. The in vivo administration of SDF-α to rabbits with saccular aneurysms promoted endothelial-lineage cell mobilization into the peripheral blood and reendothelialization of the aneurysm wall. ConclusionsThe SDF-1α expression level in the peripheral blood and local aneurysm wall correlated with the aneurysm remodeling process in rabbits with elastase-induced saccular aneurysms. We conclude that SDF-1α may facilitate aneurysm wall remodeling by up-regulating VE-cadherin expression and mobilizing endothelial-lineage cells.

Comparative study of abdominal and thoracic aortic aneurysms: their pathogenesis and a gingival fibroblasts-based ex vivo treatment.

Aortic aneurysms (AAs) consist of slow proteolysis and loss of both collagen and elastin matrix in the aorta wall, leading to wall dilation, weakening and rupture in well-advanced lesions. This can occur in both abdominal aorta (Abdominal Aortic Aneurysm: AAA) and thoracic aorta (Thoracic Aortic Aneurysm: TAA). To date, no non-surgical therapy has been proposed to slow or stop AA progression. Previously published preclinical studies from our team using an aneurysm rabbit model showed a promising concept for treatment of AAs with gingival fibroblast (GFs) which are readily available cells. In this study, we investigated the possible tissue repair of human AAAs and TAAs using ex vivo models co-cultured with GFs. Histological analysis showed that TAA and AAA are two distinct pathologies. Both lesions presented destruction of the aorta wall, highly evidenced in AAA samples. The results have confirmed the presence of the bacterial Porphyromonas gingivalis (Pg) protein in all AAA samples, but not in TAA samples, indicating the possible role of an infectious factor in the developing and progression of AAA lesions compared to TAA. The co-culture of GFs with AA lesions shows increased expression of TIMP-1, the inhibitor of the aneurysm severity marker MMP-9. Our study indicates that GFs might ameliorate aorta wall reestablishment in both AA types by their regenerative and immunomodulatory capacities. It also demonstrates the possible infectious cause of AAA compared with TAA that may explain their different behavior.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-0976-9) contains supplementary material, which is available to authorized users.

Expression of NF-κB, MCP-1 and MMP-9 in a Cerebral Aneurysm Rabbit Model

We explored the early expression of NF-κB, MCP-1 and -MMP 9 in a rabbit carotid aneurysm model, and investigated the possible mechanism of aneurysm. twenty four adult new Zealand rabbits were divided into four groups. normal control (group a); rabbits received elastase induction for 1, 2 3 weeks (group b, C and d respectively); hematoxylin-eosin stains were performed for observation. the mrna and protein expression of NF-κB, MCP-1 and MMP-9 were analyzed using RT-PCR and immunohistochemical methods. the expression of NF-κB and MCp-1 reached their peaks after induction for one week, then decreased. their expression in week 1 and week 2 had no statistical difference. the expression of MMP-9 increased after induction. We observed the highest expression at week 3. as the induction time increased, the number of smooth muscles reduced. endothelial cells were damaged; the aneurysm wall elastic layer was damaged. activation of NF-κB may be one of the initiating factors contributing to the occurrence and development of cerebral aneurysm. MCP-1 induced macrophage adhesion and infiltration in the artery wall of cerebral aneurysms, and contributed to the occurrence and development of brain aneurysm. damage to elastic fibers is one of the key factors for aneurysm formation. increased infiltration of inflammatory cells and the secretion of MMP-9 are the main reasons for elastic fiber damage.

An improved elastase-based method to create a saccular aneurysm rabbit model

Purpose. To find a safe, effective, and simple method to create a rabbit aneurysm model. Methods. Twelve adult New Zealand rabbits were divided into two groups: experimental (n = 9) and control (n = 3). The origin of the right external carotid artery was occluded with a temporary aneurysm clip, after which the right external carotid artery was ligated distally. The resulting stump was infused with elastase (experimental group) or saline (control group) for 20 minutes, and the clip was removed. The animals were studied angiographically and sacrificed 3 weeks after the procedure to harvest the aneurysms for histological analysis. Results. All nine rabbits in the experimental group successfully developed aneurysm after 3 weeks. Aneurysms had an average height of 5.2 ± 1.1 mm and width of 3.5 ± 0.8 mm. Histological analysis showed that the tunica media of the aneurysmal wall was barely identifiable. None of the three rabbits in the control group developed an aneurysm, and instead had achieved closure of the right external carotid artery stump. Conclusions. We have established an effective and a simple elastase-based method to create a rabbit aneurysm model. The procedure is easy to perform and does not require an interventional technique and or ligation of the internal carotid artery, which would otherwise reduce the blood supply to the brain.

The effects of the expression of NF - kB, MCP - 1 and MMP - 9 on experimental cerebral aneurysm rabbit model

Objective To study the effects of nuclear factor Kappa B (NF - κB),MCP - 1 and MMP -9 at the early phase of cerebral aneurysm (CA).Methods 24 healthy New Zealand rabbits,half female and half male,were randomly divided into 4 groups:group A ( control group),group B ( 1 week),group C(2 weeks),group D (3 weeks),6 rabbits per-group.The morphologic change of the right common carotid artery and formation of the aneurysm were detected by CT angiography and HE dyeing.Aneurysm samples were collected,and immunohistochemistry and real - time rolymerase chain reaction ( Real - time PCR)used to detect the expression of the proteinum and mRNA of NF - κB,MCP - 1 and MMP -9.Results ( 1 ) After a week,using CT angiography to detect all the 18 experimental rabbits,all of them have found visible fusiform or cystiform aneurysms where the elastase was dropped,and also found that some vessels were obstructed.Aneurysms have not found in all the control group rabbits.The pathological examination of the experimental aneurysms showed that the wall of aneurysm becoming thinner,the internal elastic layers were disrupted or disappeared and the reduced medial vascular smooth muscle cell becoming atrophy or degradation obviously.Inflammatory cell infiltrate were also observed in the control group,but the internal elastic layers degradation and vascular smooth muscle degeneration were not found.(2)The result of immunohistochemistry and Real - time PCR indicate that NF - κB and MCP - 1 reached the peak at 1 week,and decreased at 3 weeks.MMP - 9 was increased gradually.The expression of NF - κB and MCP - 1 were not found in control group.Conclusion NF - κB activation may be one of the initiating agents in the development of the cerebral aneurysm.MCP - 1 and MMP - 9 significantly increased in CA that play an important role in the pathogenesis of cerebral aneurysm(CA). Key words: Aneurysm; Nuclear factor - κB; Monocyte chemotactic protein - 1; MMP -9