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

Abstract

BackgroundDisease 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.MethodsWe 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).ConclusionsWe 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.

UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: Questionnaire and workshop proceedings

“…From these sources the predominant models and approaches were rodent, for example in our literature review only 2% of relevant VCI studies used non-rodent models. This finding is in keeping with other recent reviews of VCI models, where the non-rodent models were all larger species (eg ruminants) 42 . The potential differences between mouse and rat VCI models was not a major feature of our review or others 55 suggesting that these differences are perceived as less important than other factors in the VCI community.…”

“…Some participants felt that aspects of executive function could be assessed in mice, using attentional control, working memory, rule learning and reversal-based assessment. Some other laboratories are developing models in other larger species such as pig 42 .…”

A New Rat Model of Chronic Cerebral Hypoperfusion Resulting in Early-Stage Vascular Cognitive Impairment

“…According to established standards in the field (Venkat et al, 2015;Hainsworth et al, 2017), the main purpose of establishing an animal model of vascular cognitive impairment is to replicate the pathological process of human cognitive impairment. In the present study, the main goal was to replicate the pathological process of white matter damage; this process combines the decline in vascular circulation and the age-dependent narrowing of the carotid arteries.…”

Vascular neurocognitive disorders and the vascular risk factors

“…However, there may be a connection between cerebral bleedings and NCD, depending on its localization and/or dimension, or in the case of cortical and subcortical hemorrhages, whether the patient had arterial hypertension antecedents. According to several hypotheses, several mechanisms might explain the appearance and development of certain neurocognitive disorders for patients affected by a stroke, such as (5,6,12): o the cerebral injuries determined by an ischemic or hemorrhagic stroke, involving neurological deficits (motor deficits, sensitivity, language or sight disorders, etc.) can result in perturbations of superior nervous functions, having as clinical expression minor or major neurocognitive disorders; o after an ischemic or hemorrhagic stroke, the neurocognitive disorder may actually be a continuation of a preexistent state, such as the Alzheimer dementia, not made known by the patient, or not diagnosed before the cerebrovascular event; o the recidivated ischemic stroke can lead to the development of the neurocognitive disorders; as is well known, multiple ischemic attacks can favor the development of certain cognitive disorders characterized by a rapid progressive model (multi infarction dementia).…”