Translational models for vascular cognitive impairment: A review including larger species

Atticus H. Hainsworth*, Stuart M. Allan, Johannes Boltze, Catriona Cunningham, Chad Farris, Elizabeth Head, Masafumi Ihara, Jeremy D. Isaacs, Raj N. Kalaria, Saskia A.M.J. Lesnik Oberstein, Mark B. Moss, Björn Nitzsche, Gary A. Rosenberg, Julie W. Rutten, Melita Salkovic-Petrisic, Aron M. Troen

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

76 Scopus citations

Abstract

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.

Original languageAmerican English
Article number16
JournalBMC Medicine
Volume15
Issue number1
DOIs
StatePublished - 25 Jan 2017

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2017 The Author(s).

Keywords

  • Experimental models
  • In vivo models
  • Translational models
  • VCID
  • Vascular cognitive impairment
  • Vascular dementia

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