Deeper Cerebral Hypoperfusion Leads to Spatial Cognitive Impairment in Mice

Background: Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.

Methods: Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.

Results: These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05).

Conclusion: We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.