Pan William Wei-Lin, Itani Masahiko, Karagiozov Kostadin, Komatsu Teppei, Ohta Hiroki, Koseki Hirokazu, Hataoka Shunsuke, Arakawa Yoshiki, Okano Hirotaka James, Aoki Tomohiro, Murayama Yuichi
Department of Neurosurgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan.
Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan.
Transl Stroke Res. 2025 Jul 16. doi: 10.1007/s12975-025-01366-w.
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 . 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.
颅内动脉瘤(IAs)是自发性蛛网膜下腔出血(SAH)的主要原因,且与高发病率和死亡率相关。当前的IA啮齿动物模型通常破裂率较低且成像能力有限,限制了它们的转化应用价值。本研究引入了一种基于弹性蛋白酶的改良大鼠模型,该模型结合了血管造影成像以克服这些挑战。使用手术和药物干预相结合的方法在7周龄雌性Sprague-Dawley大鼠中诱导IAs,包括颈动脉和肾动脉结扎、双侧卵巢切除术、高盐饮食以及向基底池注射两次弹性蛋白酶。采用数字减影血管造影(DSA)评估动脉瘤的形成和破裂率。进行组织学和免疫组织化学分析以表征动脉瘤形态和炎症反应。改良后的模型在28天内实现了较高的IA形成率(85%)和破裂率(60%)。DSA能够可视化血管迂曲和血流动力学,这些特征与人类IA的发展相关,人类IA通常发生在承受血流动力学应力的区域,并且颅内血管的迂曲会影响其破裂。组织学分析表明动脉瘤壁存在结构降解,而免疫组织化学显示有中性粒细胞浸润,这可能意味着炎症与IA破裂有关。这种改良的IA模型为诱导和可视化具有高破裂率的IAs提供了一种可靠的方法,使其成为研究IAs病理生理学和治疗干预的有价值工具。通过DSA增强后,该模型有潜力通过实时监测动脉瘤的发展和破裂来推进治疗研究。