Moyamoya disease (MMD) is an intracranial steno-occlusive pathology characterized by progressive narrowing of proximal large vessels, including the terminal internal carotid arteries (ICAs), middle cerebral arteries, or anterior cerebral arteries. Named for the “puff of smoke” appearance of the anomalous vascularization visualized on cerebral angiography, MMD lacks a well-defined etiology, although significant insights have been made, including the identification of a susceptibility gene, RNF213, in humans with the disease. A limitation to advancing the understanding and treatment of MMD has been the lack of experimental animal models that authentically reflect the clinical pathogenesis. In an effort to analyze characteristics of currently available models and identify strategies for future model generation, the authors performed a scoping review of experimental animal models that have been used to study MMD.

A systematic search of PubMed, Web of Science, and Scopus was performed to identify articles describing animal models used to study MMD. Additional articles were identified via citation searching. Study selection and data extraction were performed by two independent reviewers based on defined inclusion and exclusion criteria.

A total of 44 articles were included for full-text review. The methods used to generate these animal models were broadly classified as surgical (n = 25, 56.8%), immunological (n = 7, 15.9%), genetic (n = 6, 13.6%), or a combination (n = 6, 13.6%). Surgical models typically involved permanent ligation of one or both of the common carotid arteries or ICAs to produce chronic cerebral hypoperfusion. Genetic models utilized known MMD or cerebrovascular disease-related genes, such as RNF213 or ACTA2, to induce heritable cerebral vasculopathy. Finally, immunological models attempted to induce vasculitis-type pathology by recapitulating the inflammatory milieu thought to underlie MMD.

Models generated for MMD have involved three general approaches: surgical, immunological, and genetic. Although each reflects a key aspect of MMD pathogenesis, the failure of any individual model to recapitulate the development, progression, and consequences of the disease underscores the importance of future work in developing a multietiology model.

烟雾病 (MMD) 是一种颅内狭窄闭塞病理，其特征是近端大血管进行性变窄，包括颈内动脉 (ICA)、大脑中动脉或大脑前动脉。MMD 以脑血管造影显示的异常血管化的“冒烟”外观命名，缺乏明确的病因，尽管已经取得了重要的见解，包括易感基因RNF213 的鉴定，在患有这种疾病的人中。促进对 MMD 的理解和治疗的一个限制是缺乏真实反映临床发病机制的实验动物模型。为了分析当前可用模型的特征并确定未来模型生成的策略，作者对用于研究 MMD 的实验动物模型进行了范围审查。

对 PubMed、Web of Science 和 Scopus 进行了系统搜索，以确定描述用于研究 MMD 的动物模型的文章。通过引文搜索确定了其他文章。研究选择和数据提取由两名独立审查员根据定义的纳入和排除标准进行。

共有44篇文章被纳入全文审查。用于生成这些动物模型的方法大致分为手术 (n = 25, 56.8%)、免疫学 (n = 7, 15.9%)、遗传学 (n = 6, 13.6%) 或组合 (n = 6, 13.6%）。手术模型通常涉及永久结扎颈总动脉或 ICA 中的一个或两个以产生慢性脑灌注不足。遗传模型利用已知的 MMD 或脑血管疾病相关基因，如RNF213或ACTA2，诱导可遗传的脑血管病。最后，免疫模型试图通过概括被认为是 MMD 基础的炎症环境来诱导血管炎型病理。

为 MMD 生成的模型涉及三种一般方法：手术、免疫和遗传。尽管每个都反映了 MMD 发病机制的一个关键方面，但任何单个模型都无法概括疾病的发展、进展和后果，这强调了未来开发多病因模型的重要性。