Animal Models of Chronic Cerebral Hypoperfusion: From Mouse to Primate

Abstract

Vascular cognitive impairment (VCI) or vascular dementia occurs as a result of brain ischemia and represents the second most common type of dementia after Alzheimer’s disease. To explore the underlying mechanisms of VCI, several animal models of chronic cerebral hypoperfusion have been developed in rats, mice, and primates. We established a mouse model of chronic cerebral hypoperfusion by narrowing the bilateral common carotid arteries with microcoils, eventually resulting in hippocampal atrophy. In addition, a mouse model of white matter infarct-related damage with cognitive and motor dysfunction has also been established by asymmetric common carotid artery surgery. Although most experiments studying chronic cerebral hypoperfusion have been performed in rodents because of the ease of handling and greater ethical acceptability, non-human primates appear to represent the best model for the study of VCI, due to their similarities in much larger white matter volume and amyloid β depositions like humans. Therefore, we also recently developed a baboon model of VCI through three-vessel occlusion (both the internal carotid arteries and the left vertebral artery). In this review, several animal models of chronic cerebral hypoperfusion, from mouse to primate, are extensively discussed to aid in better understanding of pathophysiology of VCI.

WITHDRAWN: Mitochondrial accumulation induced axon dysfunction promotes paranode instability and demyelination in hypoxic-ischemic forms of demyelination

“…In hypoxic-ischemic forms of demyelination, loss of oligodendrocytes has been noticed and obvious axonal injuries have also been reported by other studies 1,2 . Unlike immune-mediated demyelinating diseases ( e.g.…”

“…Time-lapse imaging using confocal microscopy Mitochondria were labelled with CMXRos after brain slices were treated with LGLO. The distribution, size, and mean transport velocity of CMXRos-positive mitochondria in myelinated and demyelinated Purkinje cell axons were imaged using the Olympus inverted confocal microscope as described previously 2 .…”

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

“…Based on these previous studies and our results, we suggest that the loss of the EG in capillaries, caused by the pathological progression of SVaD, may induce greater leukocyte adhesion to the vascular endothelium and, thereby, promote capillary stalling. In the SVaD model used in this study, the gradual decrease in arterial flow speed and pulsatility index, which is influenced by artery inflow and vessel resistance, was followed by impaired microcirculation ( Supplementary Figure 2) 31,32 . Since the production and maintenance of the EG closely correlates with fluid shear stress, it is plausible that the decreased capillary flow speed may be a primary factor affecting the EG loss 25,33,34 .…”

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

“…A chronic decline in sustained cerebral blood flow is the main mechanism underlying the development of vascular cognitive impairment (VCI) (Kazumata et al, 2019;Kim et al, 2019;Mansour et al, 2019;McKetton et al, 2019). Thus, animal models of chronic cerebral hypoperfusion are most commonly used to study VCI (Duncombe et al, 2017;Mansour et al, 2018;Washida et al, 2019).Therefore, our future studies aim to combine age factors with chronic cerebral hypoperfusion allowing the exploration of changes in the white matter and cognitive functions in elderly rats under different degrees of hypoperfusion and to establish a new VCI model of elderly rats with bilateral common carotid artery (CCA) stenosis (BCAS).…”