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Folia Neuropathologica
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2/2022
vol. 60
 
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abstract:
Original paper

Effects of ischemia-hypoperfusion on neuro-vascular units in dual transgenic mice with Alzheimer’s disease

Linjuan Sun
1
,
Chengfu Li
2
,
Jiangang Liu
1
,
Nannan Li
1
,
Fuhua Han
3
,
Dandan Qiao
1
,
Zhuang Tao
4
,
Min Zhan
1
,
Wenjie Chen
1
,
Yunling Zhang
1
,
Xiaoying Zheng
5

  1. Department of Neurology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, P.R. China
  2. China Population and Development Research Center, Beijing, P.R. China
  3. Beijing University of Chinese Medicine, Beijing, P.R. China
  4. China Academy of Chinese Medical Sciences, Beijing, P.R. China
  5. Department of Institute of Population Research, Peking University, Beijing, P.R. China
Folia Neuropathol 2022; 60 (2): 237-249
DOI: https://doi.org/10.5114/fn.2022.117278
Online publish date: 2022/06/30
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Introduction
The study aimed to investigate the effects of ischemia on neuro-vascular units in transgenic mice, and to investigate the role of ischemia-hypoperfusion in the model of dual transgenic mice with dementia.

Material and methods
In this study, the ischemic model was generated by operating a bilateral common carotid artery micro-embolism. Mice were divided into four groups, including group 1: C57BL sham surgery group (control), group 2: C57BL ischemic group, group 3: amyloid precursor protein/presenilin-1 (APP/PS1) group, and group 4: APP/PS1 ischemic group. Each group comprised 20 mice. Spatial behavior and memory ability of mice were detected by Morris water maze and jumping platform test. Mouse hippocampus was observed by HE staining and Congo red staining. Ultrastructure of each group of neuro-cyclic units was observed by electron microscopy. Various biochemical indicators were detected by ELISA. Western blot detected the amount of protein expression. qRT-PCR identified mRNA expression.

Results
The results indicated that learning and memory functions of C57 ischemic mice were lower than those of control group. Positive expression area of APP in APP/PS1 ischemic group was higher than in APP/PS1 group. In APP/PS1 group and APP/PS1 ischemic group, the content of Ab was significantly higher than in C57 ischemic group. Electron microscopic observation revealed that there were more mitochondrial vacuoles in hippocampal neurons of APP/PS1 mice, and the structure was relatively intact. Mitochondrial vacuoles in hippocampus increased significantly, and vascular wall proliferated in APP/PS1 ischemic group. Compared with C57 control group, the content of vascular endothelial growth factor (VEGF) increased significantly in C57 ischemic group.

Conclusions
Ischemia deteriorates the learning and memory function of transgenic mice, aggravates the damage of neuro-vascular units, and impairs the blood–brain barrier transport of Ab, leading to an increase in the concentration of Ab cerebrospinal fluid, and further deterioration of neuro-vascular units. At the same time, ischemia is an effective stimulating factor in the release of VEGF.

keywords:

hypoperfusion, Alzheimer’s disease, transgenic mice, neuro-vascular unit, ischemia-hypoperfusion
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