Rodent Models of Vascular Cognitive Impairment
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Rodent Models of Vascular Cognitive Impairment Qing‑zhang Tuo1 · Jin‑jun Zou1 · Peng Lei1 Received: 24 September 2020 / Accepted: 12 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Vascular cognitive impairment (VCI) refers to the entire spectrum of vascular brain pathologies that contribute to cognitive deficits, ranging from subjective cognitive decline to dementia. The main pathologies in VCI are infarcts and white matter hyperintensities due to ischemia. VCI rodent models can be divided into surgical models (e.g., MCAO, BCAO, BCAS, 2-VO, 4-VO) and genetic models (e.g., SHR/SP, T2DM, CAA, CADASIL) based on construction methods. However, no single model can fully recapitulate the pathogenesis of VCI, and choosing the appropriate model for different research purposes would be of crucial importance. Here, we have summarized the commonly used rodent VCI models and discussed their advantages and limitations to provide a necessary reference for selecting suitable animal models to investigate the molecular pathways involved in VCI and develop therapeutic interventions. Keywords Vascular cognitive impairment · Dementia · Alzheimer’s disease · Chronic global hypoperfusion · MCAO · SHR/SP
Introduction Vascular cognitive impairment (VCI) refers to a complex neurological disorder that presents with vascular pathology and cognitive impairment (van der Flier et al. 2018). The degree of both vascular pathology and cognitive decline can vary from case to case, resulting from brain parenchymal changes such as macro- and microinfarcts, hemorrhages, white matter changes, and brain atrophy occurring in an aging brain. The risk factor of VCI is similar to cerebral ischemia, which includes hypertension, diabetes, obesity, and dyslipidemia (van der Flier et al. 2018). Therefore, the precise pathophysiological mechanisms of VCI remain unclear. While most of the dementia research is focused on Alzheimer’s disease (AD), there is a growing interest for VCI, since it can represent 50–70% cases of dementia, including AD with a vascular component (van der Flier et al. 2018). The main cerebrovascular pathologies in VCI are infarcts and white matter hyperintensities due to ischemia (Gorelick * Peng Lei [email protected] 1
Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
et al. 2011), and the current VCI animal models are all based on cerebral ischemia. However, so far, no animal model can comprehensively mimic the pathogenesis of VCI (Jiwa et al. 2010). Knowing the advantage and disadvantages of different animal models and choosing the appropriate ones according to the purpose of the study is challenging but of critical importance. Rodents are the most common type of animals used for VCI models (Table 1). In this review, we summarize the conventional rodent VCI models, including surgical models and genetic models, and elaborate on each model’s application range.
Surgical animal models Transient
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