Background: 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.
Methods: 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).
Conclusions: 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.
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AHH gratefully acknowledges funding from Alzheimer’s Drug Discovery Foundation (ADDF grant no. 20140901), Alzheimer’s Society UK (PG146/151) and Alzheimer’s Research UK (PPG2014A-8). SMA received research funding from the British Heart Foundation and EPSRC (UK). CC is funded by the MRC (UK) Centre for Doctoral Training in Regenerative Medicine (grant no. EP/L014904/1). AMT was supported in this work by Israel Science Foundation (ISF) Grant 1353/11.
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; and Troen, Aron M., "Translational Models for Vascular Cognitive Impairment: A Review Including Larger Species" (2017). Pharmacology and Nutritional Sciences Faculty Publications. 50.