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Experimental animal models for moyamoya disease and treatment: a pathogenesis-oriented scoping review

机译:烟雾病和治疗的实验动物模型:以发病机制为导向的范围研究综述

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OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
机译:目的 烟雾病(MMD)是一种颅内狭窄闭塞性病变,其特征是近端大血管进行性狭窄,包括颈内动脉末梢(ICA)、大脑中动脉或大脑前动脉。MMD因脑血管造影上可见的异常血管形成的“烟雾”外观而得名,缺乏明确的病因,尽管已经取得了重要的见解,包括鉴定出易感基因RNF213,在患有该疾病的人类中。推进对MMD的理解和治疗的一个局限性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。方法 对 PubMed、Web of Science 和 Scopus 进行系统检索,以确定描述用于研究 MMD 的动物模型的文章。通过引文检索确定了其他文章。研究筛选和资料提取由两名独立评价员根据定义的纳入和排除标准进行。结果 共纳入44篇全文。用于生成这些动物模型的方法大致分为外科(n = 25,56.8%),免疫学(n = 7,15.9%),遗传(n = 6,13。6%)或组合(n = 6,13.6%)。手术模型通常涉及对一条或两条颈总动脉或 ICA 进行永久性结扎,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,诱导遗传性脑血管病变。最后,免疫学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学。结论 MMD模型的生成涉及三种一般方法:手术、免疫和遗传。尽管每个模型都反映了MMD发病机制的一个关键方面,但任何单个模型都未能概括疾病的发展、进展和后果,这凸显了未来工作在开发多病因学模型方面的重要性。

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