Table_1_A New Rat Model of Chronic Cerebral Hypoperfusion Resulting in Early-Stage Vascular Cognitive Impairment.DOCX

ObjectiveCurrently, most models of vascular cognitive impairment are established by occluding the carotid arteries uni- or bilaterally to reduce the cerebral blood flow mimicking chronic cerebral hypoxia. Due to the sudden blood flow interruption, a gradual narrowing of the carotid artery cannot be completely imitated. This paper aims to establish a bilateral carotid stenosis model with mild cognitive dysfunction and mild white matter changes to simulate patients with vascular predementia.
MethodsAged Wistar rats (18 months old) underwent either bilateral common carotid artery stenosis (BCAS) or occlusion (BCAO) surgery or a sham operation (control group). The cerebral blood flow in the frontal cortex was measured using Doppler flowmetry. Thirty days after surgery, cognitive function impairments were determined with the Morris water maze; cerebral magnetic resonance imaging was performed to detect changes in fractional anisotropy to assess white matter injuries, and histological studies were performed.
ResultsThe aged rats in the BCAS group showed a more gradual cerebral blood flow reduction and a lower mortality rate (11%) compared to rats in the BCAO group. The water maze test revealed a more marginal impairment affecting spatial learning and memory in rats with BCAS than in rats with BCAO. Diffusion tensor imaging detected white matter injuries in the hippocampus and cerebral cortex of BCAS rats. Particularly, a small portion of nerve fibers of the lateral somatosensory cortex was significantly different between rats of the BCAO and BCAS groups. In the BCAS group, the microscopic structure of the hippocampal CA1 region changed slightly after 30 days and sustained a slight mitochondrial crista crack. Fluorescence staining indicated that the number of GFAP-positive cells was increased in rat brains of the BCAS group, and this phenomenon was even more pronounced in the BCAO group. The hnRNPA2/B1 and GABAAR-α1 expression levels were significantly decreased in the hippocampus of rats with BCAS compared to those of controls.
ConclusionSevere bilateral carotid stenosis induced mild cognitive dysfunction and slight structural changes in the brains of aged rats. Thus, a chronic cerebral hypoperfusion model was successfully established.

研究背景与目的：目前，多数血管性认知障碍模型通过单侧或双侧结扎颈动脉以降低脑血流量，以此模拟慢性脑低氧状态。但该方法会导致血流突然中断，无法完全模拟颈动脉渐进性狭窄的病理过程。本研究旨在构建兼具轻度认知功能障碍与轻度白质病变的双侧颈动脉狭窄模型，以模拟血管性痴呆前期患者的病理状态。

方法：选用18月龄的老年Wistar大鼠，随机分为双侧颈总动脉狭窄（BCAS）组、双侧颈总动脉结扎（BCAO）组及假手术对照组。采用多普勒血流仪检测大鼠额叶皮层的脑血流量。术后30天，通过莫里斯水迷宫检测大鼠的认知功能损伤情况；通过脑磁共振成像检测各向异性分数变化以评估白质损伤，并开展组织学检测。

结果：与BCAO组大鼠相比，BCAS组老年大鼠的脑血流量呈更渐进性的下降趋势，且死亡率更低（11%）。莫里斯水迷宫测试结果显示，BCAS组大鼠的空间学习记忆能力受损程度较BCAO组更轻微。弥散张量成像结果显示，BCAS组大鼠海马体与大脑皮层存在白质损伤；其中，躯体感觉皮层外侧区的部分神经纤维在两组间存在显著差异。术后30天，BCAS组大鼠海马CA1区的显微结构发生轻度改变，并伴随轻微的线粒体嵴断裂现象。荧光染色结果显示，BCAS组大鼠脑内胶质纤维酸性蛋白（GFAP）阳性细胞数量增加，且该现象在BCAO组中更为显著。与对照组相比，BCAS组大鼠海马体内异质性细胞核核糖核蛋白A2/B1（hnRNPA2/B1）与γ-氨基丁酸A型受体α1亚基（GABAAR-α1）的表达水平显著降低。

结论：双侧颈总动脉狭窄可诱导老年大鼠出现轻度认知功能障碍与轻微脑结构改变，本研究成功构建了慢性脑低灌注模型。