Hainsworth Atticus H, Allan Stuart M, Boltze Johannes, Cunningham Catriona, Farris Chad, Head Elizabeth, Ihara Masafumi, Isaacs Jeremy D, Kalaria Raj N, Lesnik Oberstein Saskia A M J, Moss Mark B, Nitzsche Björn, Rosenberg Gary A, Rutten Julie W, Salkovic-Petrisic Melita, Troen Aron M
Clinical Neurosciences (J-0B) Molecular and Clinical Sciences Research Institute, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK.
Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.
BMC Med. 2017 Jan 25;15(1):16. doi: 10.1186/s12916-017-0793-9.
Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.
We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations).
We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required.
疾病模型对于病理学的前瞻性研究、分子和细胞机制的鉴定、干预措施的临床前测试以及临床生物标志物的验证很有用。在此，我们综述与血管性认知障碍（VCI）相关的动物模型。每个模型的概要最初由专业从业者呈现。概要由作者进行完善，随后由近期一次会议（2015年血管性痴呆国际会议）的科学委员会进行完善。仅引用了经过同行评审的资料来源。
我们纳入了模拟与VCI相关的脑损伤（白质灌注不足损伤、局灶性缺血、脑淀粉样血管病）或重现VCI危险因素（老年、高血压、高同型半胱氨酸血症、高盐/高脂饮食）或重现VCI遗传病因（导致CADASIL的Notch3突变）的模型。
我们得出以下结论：（1）转化模型可能反映与VCI相关的病理过程，但不能完全复制人类疾病谱；（2）VCI的啮齿动物模型受到白质缺乏的限制；（3）需要进一步的转化模型以及改进的认知测试工具。
