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双侧颈总动脉狭窄小鼠模型中的早期海马功能和结构损伤

Early functional and structural hippocampal impairment in a bilateral common carotid artery stenosis mouse model.

作者信息

Tang Ping, Sun Yi, Yang Chunsheng, Zhang Nan

机构信息

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

Department of Neurology, Tianjin Medical University General Hospital Airport Site, Tianjin, China.

出版信息

Animal Model Exp Med. 2025 Jun;8(6):1033-1043. doi: 10.1002/ame2.12549. Epub 2025 Jan 23.

DOI:10.1002/ame2.12549
PMID:39853719
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12205007/
Abstract

BACKGROUND

Subcortical ischemic vascular dementia (SIVD) is a common subtype of vascular dementia. Currently, the bilateral common carotid artery stenosis (BCAS) mouse model is the most suitable SIVD rodent model. In this study, we investigated the functional and structural impairments in the hippocampus 1 month after BCAS.

METHODS

We used behavioral tests, laser speckle flowmetry, long-term potentiation, histochemical staining, molecular experiments, and voxel-based morphometry to evaluate the hippocampal impairments.

RESULTS

Behavioral studies revealed that BCAS mice exhibited worse performance. Laser speckle flowmetry detected an obvious decrease in cerebral blood flow. The synaptic plasticity of the perforant path-dentate gyrus pathway was inhibited. Decreased fractional anisotropy and increased mean diffusivity were detected in the hippocampus via diffusion tensor imaging data. A reduction in gray matter volume, which was most prominent in the hippocampus and its surrounding areas, was detected via voxel-based morphometry analysis. Impairments in cell morphology and myelin integrity were validated using histochemical staining and molecular biology techniques. In addition, the numbers of GFAP astrocytes and Iba1 microglia increased in the hippocampus.

CONCLUSIONS

Overall, our study demonstrates early functional and structural impairments in the hippocampus contributing to learning and memory deficits after 1 month of BCAS, indicating that the hippocampus is vulnerable to chronic cerebral ischemia.

摘要

背景

皮质下缺血性血管性痴呆（SIVD）是血管性痴呆的一种常见亚型。目前，双侧颈总动脉狭窄（BCAS）小鼠模型是最适合的SIVD啮齿动物模型。在本研究中，我们调查了BCAS术后1个月海马体的功能和结构损伤。

方法

我们使用行为测试、激光散斑血流仪、长时程增强、组织化学染色、分子实验和基于体素的形态测量法来评估海马体损伤。

结果

行为学研究表明，BCAS小鼠表现较差。激光散斑血流仪检测到脑血流量明显减少。穿通通路-齿状回通路的突触可塑性受到抑制。通过扩散张量成像数据在海马体中检测到分数各向异性降低和平均扩散率增加。通过基于体素的形态测量分析检测到灰质体积减少，在海马体及其周围区域最为明显。使用组织化学染色和分子生物学技术验证了细胞形态和髓鞘完整性的损伤。此外，海马体中GFAP星形胶质细胞和Iba1小胶质细胞的数量增加。

结论

总体而言，我们的研究表明，BCAS术后1个月海马体早期出现功能和结构损伤，导致学习和记忆缺陷，表明海马体易受慢性脑缺血影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b00/12205007/01e9310b6f3c/AME2-8-1033-g001.jpg
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