Modified Intracranial Aneurysm Rupture Rat Model with Angiographic Imaging

Abstract

Intracranial aneurysms (IAs) are a major cause of spontaneous subarachnoid hemorrhage (SAH) and are associated with high morbidity and mortality. Current IA rodent models often exhibit low rupture rates and limited imaging capabilities, restricting their translational utility. This study introduces a modified elastase-based rat model that incorporates angiographic imaging to overcome these challenges. IAs were induced in 7-week-old female Sprague-Dawley rats using a combination of surgical and pharmacological interventions, including carotid artery and renal artery ligation, bilateral ovariectomy, high-salt diet, and two elastase injections into the basal cistern. Digital subtraction angiography (DSA) was employed to assess aneurysm formation and rupture rate. Histological and immunohistochemical analyses were conducted to characterize aneurysm morphology and the inflammatory response. The modified model achieved a high rate of IA formation (85%) and rupture (60%) within 28 days. DSA enabled visualization of vessel tortuosity and flow dynamics, features relevant to human IA development, which often occurs in areas subjected to hemodynamic stress, and the tortuosity of intracranial vessels affects their rupture ^[1]. Histological analysis indicated structural degradation of the aneurysm wall, while immunohistochemistry showed neutrophil infiltration, potentially implicating inflammation in IA rupture. This improved IA model offers a reliable method for inducing and visualizing IAs with a high rupture rate, making it a valuable tool for studying the pathophysiology and therapeutic interventions of IAs. Enhanced by DSA, this model has the potential to advance therapeutic research by enabling the real-time monitoring of aneurysm development and rupture.

Keywords: Digital subtraction angiography; Hemodynamic force; Intracranial aneurysms; Rat model; Subarachnoid hemorrhage.