Abstract DP073: Novel Rat Model of Intracranial Aneurysm Reproducing Human Pathology for Preclinical Endovascular Device Evaluation

Introduction: Intracranial aneurysms (IAs) are treated with endovascular devices. Although large animal models are valuable for device development, they are costly, can only reproduce the morphological aspects of IAs, and fail to replicate human IA histopathology. A small-animal model that reproduces human IA pathology, while allowing clinically relevant interventions, could provide a cost-effective and practical platform for device evaluation. Methods: Seven-week-old male Sprague–Dawley rats underwent end-to-side anastomoses of the common carotid artery to create a new bifurcation site. An irreversible lysyl oxidase inhibitor was administered to promote the degeneration of the aneurysm wall. Aneurysm formation was evaluated using femoral artery angiography and histopathology. Selected lesions were treated with coil embolization using clinical microcatheters and platinum coils. The volumetric embolization ratio (VER) was calculated, and the healing process was assessed histologically. Results: Two weeks postoperatively, 70% of the animals developed saccular aneurysms (3–5 mm) at the newly created bifurcations; approximately one third of these ruptured spontaneously. Histopathological and immunohistochemical analyses reproduced the hallmark features of human IA, including endothelial cell loss, medial thinning, and inflammatory infiltration. Coil embolization was successful in 75% of treated aneurysms. Preliminary findings indicated that aneurysms with VERs ≤20% ruptured within 2 weeks of embolization and exhibited no histological healing at 4 weeks, while aneurysms with higher VERs were associated with stable occlusion and progressive organization. The sequence of healing after coiling, characterized by inflammatory cell infiltration, fibrocellular ingrowth, and neointimal formation, mirrored that observed in human posttreatment pathology. Conclusions: This model replicates human pathology, permits endovascular coiling and enables detailed observation of rupture and healing processes after embolization. The observed relationship between VER and treatment durability aligns with clinical findings, highlighting the model’s value for evaluating novel endovascular devices and exploring recurrence prevention strategies. Its cost-effectiveness, reproducibility, and compatibility with catheter-based interventions make it a robust preclinical platform that bridges the gap between experimental research and clinical applications.