深度脑灌注不足导致小鼠空间认知障碍。
Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice.
机构信息
Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China.
Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Stroke Vasc Neurol. 2022 Dec;7(6):527-533. doi: 10.1136/svn-2022-001594. Epub 2022 Jul 11.
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.
背景
血管性认知障碍（VCI）是全球第二大痴呆症病因，由脑血管疾病或相关危险因素引起。然而，目前尚无合适的动物模型可用于研究人类 VCI 神经病理学的变化。为了更好地了解 VCI 的发展，我们修改了三种慢性血管疾病的小鼠模型，并进一步比较了这些模型的优缺点。我们希望建立一个更适合模拟人类 VCI 的小鼠模型。
方法
使用成年雄性 C57/BL6 小鼠（n=98），动物分别接受短暂双侧颈总动脉闭塞（tBCCAO）、双侧颈总动脉狭窄（BCAS）或右侧单侧颈总动脉闭塞。检测表面脑血流（CBF）的血流动力学变化，直至术后 4 周。评估空间参考记忆障碍以确定慢性脑缺血的后果。
结果
与对照组相比，这些小鼠模型在术后 1 周至 4 周时显示出不同程度的 CBF 减少和空间参考记忆障碍（p<0.05）。我们发现：（1）双侧颈总动脉结扎导致 C57/BL6 小鼠 CBF 减少 90%（p<0.05），并导致急性而非慢性空间参考记忆障碍（p<0.05）；（2）单侧颈总动脉结扎不会引起 tBCCAO 小鼠那样的严重同侧缺血，只会引起轻微但显著的空间参考记忆障碍（p<0.05）；（3）双侧 CBF 减少 20%不会导致术后 4 周时空间参考记忆障碍（p>0.05），而双侧或单侧 CBF 减少 30%会导致小鼠记忆障碍显著（p<0.05）。
结论
我们证明，使用 0.16/0.18mm 微线圈的 BCAS 是研究 VCI 发病机制和开发治疗方法的替代 VCI 小鼠模型。
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