Background

Vascular cognitive impairment (VCI) refers to cognitive alterations related to vascular disease and is associated with various types of dementia [1]. Chronic cerebral hypoperfusion (CCH)-associated small vessel disease is one of the major contributors to VCI [2,3]. CCH is elicited by aging and various lifestyle diseases, such as metabolic syndromes, atherosclerosis, hypertension, obesity [4], and hypotension [5]. It has also been suggested that CCH induces white matter lesions, which are key characteristics of VCI. In addition, many patients with various types of dementia including VCI have white matter lesions [6]. To understand the precise pathological mechanism underlying CCH-induced VCI including white matter lesions, multiple rodent models have been used in many studies.

Some widely used rodent models of CCH-induced VCI are the rat bilateral common carotid artery occlusion (BCCAO), mouse unilateral common carotid artery occlusion (UCCAO), rat and mouse 2-vessel gradual occlusion (2-VGO), mouse asymmetric common carotid artery surgery (ACAS), and mouse bilateral common carotid artery stenosis (BCAS) models. However, rodent models have several limitations. First, the visual pathway is damaged and behavioral tests to assess cognitive function are affected in the rat BCCAO and mouse UCCAO models [7,8]. Second, the device used in the rat and mouse 2-VGO models and mouse ACAS model is expensive [9]. The mouse BCAS model was reported as a CCH model in 2004 by Shibata et al. [10] and is a more suitable and useful tool for research of CCH-induced VCI. This model shows cognitive impairment and a decrease in myelin sheaths without severe damage to the visual pathway [9]. In addition, BCAS-induced cognitive impairment and white matter lesions precede neuronal death [11,12]. Therefore, the mouse BCAS model reproduces the clinical picture in human VCI patients [13]. However, surgery is harder to perform in this model than in the rat BCCAO and mouse UCCAO models, and expertise is needed to create a stable mouse model. Therefore, we present a detailed and robust method that can stably create the mouse BCAS model used in our previous studies [11,12,14] for further development of VCI research.