Khan Dilaware, Li Xuanchen, Hashimoto Tomoki, Tanikawa Rokuya, Niemela Mika, Lawton Michael, Muhammad Sajjad
Department of Neurosurgery Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-Universität Düsseldorf Düsseldorf Germany.
Department of Neurosurgery and Neurobiology Barrow Neurological Institute Phoenix AZ USA.
J Am Heart Assoc. 2024 Feb 6;13(3):e031811. doi: 10.1161/JAHA.123.031811. Epub 2024 Jan 23.
Intracranial aneurysms (IAs) are rare vascular lesions that are more frequently found in women. The pathophysiology behind the formation and growth of IAs is complex. Hence, to date, no single pharmacological option exists to treat them. Animal models, especially mouse models, represent a valuable tool to explore such complex scientific questions. Genetic modification in a mouse model of IAs, including deletion or overexpression of a particular gene, provides an excellent means for examining basic mechanisms behind disease pathophysiology and developing novel pharmacological approaches. All existing animal models need some pharmacological treatments, surgical interventions, or both to develop IAs, which is different from the spontaneous and natural development of aneurysms under the influence of the classical risk factors. The benefit of such animal models is the development of IAs in a limited time. However, clinical translation of the results is often challenging because of the artificial course of IA development and growth. Here, we summarize the continuous improvement in mouse models of IAs. Moreover, we discuss the pros and cons of existing mouse models of IAs and highlight the main translational roadblocks and how to improve them to increase the success of translational IA research.
颅内动脉瘤(IAs)是一种罕见的血管病变,在女性中更为常见。IAs形成和生长背后的病理生理学很复杂。因此,迄今为止,尚无单一的药物治疗方案。动物模型,尤其是小鼠模型,是探索此类复杂科学问题的宝贵工具。IAs小鼠模型中的基因改造,包括特定基因的缺失或过表达,为研究疾病病理生理学背后的基本机制和开发新的药理学方法提供了绝佳手段。所有现有的动物模型都需要一些药物治疗、手术干预或两者兼用才能形成IAs,这与在经典危险因素影响下动脉瘤的自发和自然发展不同。此类动物模型的好处是能在有限时间内形成IAs。然而,由于IA发展和生长过程的人为因素,研究结果的临床转化往往具有挑战性。在此,我们总结了IAs小鼠模型的不断改进。此外,我们讨论了现有IAs小鼠模型的优缺点,突出了主要的转化障碍以及如何改进它们以提高IA转化研究的成功率。