A Modification to a Murine Model for Intracranial Aneurysm Formation and Rupture

Abstract

Between 3.6% and 6.0% of the population has an intracranial aneurysm. The mechanisms underlying intracranial aneurysm formation and rupture are not fully known. Several rodent models have been developed to better understand intracranial aneurysm pathophysiology. Hypertension, hemodynamic changes, and vessel injury are all necessary for aneurysm induction; however, multiple invasive procedures may disrupt an animal's physiology. Therefore, we hypothesized that our method for inducing hypertension could be modified to create a simpler model. We previously developed a highly reproducible murine model of intracranial aneurysm formation and rupture that involves hemodynamic changes through ligation of the left common carotid artery, vessel wall degradation using elastase and a lysyl oxidase inhibitor, and hypertension through a high-salt diet, continuous angiotensin II infusion, and right renal artery ligation. In order to create a simpler model, we sought to eliminate renal artery ligation. We assessed aneurysm formation, aneurysm rupture, and blood pressure in two separate cohorts of C57BL/6 mice: one cohort underwent our model as above, while another cohort did not receive right renal artery ligation. Our results demonstrate that intracranial aneurysm formation and rupture rates did not differ between each group. Further, the blood pressures between cohorts did not differ at various timepoints in the model. Both cohorts, however, did have a significant increase in blood pressure from baseline, suggesting that renal artery ligation is not needed for inducing hypertension. These findings demonstrate that our murine model can be modified to eliminate right renal artery ligation. Thus, we propose this modification to our murine model for studying intracranial aneurysm pathophysiology.

Current Mouse Models of Intracranial Aneurysms: Analysis of Pharmacological Agents Used to Induce Aneurysms and Their Impact on Translational Research

“…Hemodynamic stress is induced by using a combination of surgical strategies, including common carotid artery ligation, bilateral renal artery ligation, unilateral nephrectomy, and administration of pharmacological agents, including deoxycorticosterone or angiotensin II with increased NaCl in drinking water or food. 5 , 6 , 19 , 25 , 26 , 41 , 46 …”

“… 26 Recently, Patel et al further modified the model generated by Hosaka et al, and showed that right renal artery ligation did not affect the incidence of IA formation and rupture. 41 Starke et al developed the IA mouse model by using nephrectomy, and 1 week later, a deoxycorticosterone pellet was implanted, 1% NaCl in water was started with 0.12% β‐aminopropionitrile, and elastase (35 mU) was injected into the right basal cistern. 5 IAs were formed in 81.8% of the mice, and the incidence of ruptured IAs was observed in 68.2% of mice.…”

How to create a nervous system aneurysm model in canines? ligation of the lingual artery is a simple and effective method

“…The aneurysm model can be established by ligating the common carotid artery and inducing hypertension by injecting cortisol and diet as well, but it has the problem of uncontrollable aneurysms ( Tang et al, 2020-10 ). It has been reported that intracranial aneurysms can be induced by the degradation of the vascular wall caused by the use of elastase and lysyl oxidase inhibitors, as well as hypertension caused by a high-salt diet, continuous infusion of angiotensin II and ligation of the right renal artery, but the methods are complex and there are many uncontrollable factors ( Patel et al, 2021 ). Compared with these methods, the effect of ligating the lingual artery in dogs is accurate, and the aneurysm model can be established stably and controllably with fewer long-term complications, thereby improving the success rate of model establishment.…”

Modified Protocol for Establishment of Intracranial Arterial Dolichoectasia Model by Injection of Elastase Into Cerebellomedullary Cistern in Mice

“…Elastase is able to degrade a variety of proteins, prevent cholesterol synthesis in the body, and promote its conversion to cholicacid. In recent years, elastase has been used to induce animal models such as intracranial aneurysm, cervical common aneurysm, abdominal aortic aneurysm in rabbits, emphysema, chronic obstructive pulmonary disease, and osteoporosis ( 23 – 28 ), which can obviously induce the pathological changes of the target blood vessels and tissues with the advantages of simple, convenient and high success rate. Elastase can be extracted and purified from the animal pancreas, which pertains to the endopeptidase and contains 240 amino acid residues with the isoelectric point of 9.5 ( 29 ) and the best pH value of 8.1–8.8.…”