Pathology and Histology Assessment of Gender-Related Differences in Inflammation and Effects of Aspirin in a Rabbit Elastase-Induced Aneurysm Model

Intracranial aneurysms are a significant cause of morbidity and mortality in adults. The rabbit elastase-induced carotid artery aneurysm model is a well-established animal model that mimics human intracranial aneurysms. This model results in saccular aneurysm formation by infusion of elastase into a ligated common carotid artery stump in adult rabbits. This model closely mimics the morphology of human intracerebral aneurysms because the rabbit carotid artery is similar in size and configuration to the intracranial extent of the human carotid artery. The histopathologic appearance and hemodynamic indices, such as pressure, wall shear stress and oscillatory shear stress are similar as well. Therefore, this model presents an opportunity to study aneurysm-associated inflammatory changes as well as treatment options. Research in mice and humans has shown that aspirin has a protective effect from aneurysm rupture, although there are differences between genders. In this study, we have attempted to elucidate this in the rabbit elastase-induced aneurysm model. We hypothesized that aspirin will have a protective effect against aneurysm-associated inflammation histologically and that there will be a significant difference of this effect between males and females. 24 adult New Zealand white rabbits of both genders underwent surgery to induce a saccular carotid aneurysm. Half of the rabbits received aspirin (10 mg/kg) as a daily treatment a few weeks after surgery. Rabbits were sacrificed at ∼3–5 weeks after treatment was initiated. Initial gross necropsy findings show variability in vessel size and appearance between individuals that is not associated with aspirin treatment, but is more prevalent in female rabbits. Specifically, distended right subclavian arteries as well as neovascularization were observed and the degree of vascular abnormality varied greatly between individuals. This indicates vascular shunting in the absence of a patent carotid artery, which was not observed in the contralateral vessels. Analysis of histology using hematoxylin and eosin staining and immunohistochemistry will follow gross necropsy findings.

No conflict of interest has been declared by the author(s).