Chronic cerebral hypoperfusion facilitates lasting learning and memory impairment and induces hippocampal neurovascular unit dysfunction in rats

Yan HUANG; Jing HE; Yang XIANG; Zhiqiang WANG; Guo DU; Qingsong WANG

doi:10.16016/j.1000-5404.201803044

您当前的位置：

首页 >

文章列表页 >

Chronic cerebral hypoperfusion facilitates lasting learning and memory impairment and induces hippocampal neurovascular unit dysfunction in rats

更新时间：2026-01-09

- Chronic cerebral hypoperfusion facilitates lasting learning and memory impairment and induces hippocampal neurovascular unit dysfunction in rats
- Journal of Third Military Medical University Vol. 40, Issue 17, Pages: 1561-1567(2018)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81601112);the Scientific Research Project of Health and Family Planning Commission of Sichuan Province(16PJ014)
- DOI：10.16016/j.1000-5404.201803044
  CLC：
- Received：06 March 2018，
  
  Published：15 September 2018
- 稿件说明：
移动端阅览
Yan HUANG, Jing HE, Yang XIANG, et al. Chronic cerebral hypoperfusion facilitates lasting learning and memory impairment and induces hippocampal neurovascular unit dysfunction in rats[J]. Journal of Third Military Medical University, 2018, 40(17): 1561-1567.
DOI：

Yan HUANG, Jing HE, Yang XIANG, et al. Chronic cerebral hypoperfusion facilitates lasting learning and memory impairment and induces hippocampal neurovascular unit dysfunction in rats[J]. Journal of Third Military Medical University, 2018, 40(17): 1561-1567. DOI： 10.16016/j.1000-5404.201803044.

摘要

Abstract

Objective

To investigate the characteristics of changes in hippocampal neurovascular unit in rats after chronic cerebral hypoperfusion (CCH)

and explore the relationship of the changes of the unit with learning and memory impairment induced by CCH.

Methods

A total of 44 male adult SD rats (220~250 g) were randomly

divided into: CCH group (

=24) and control group (

=20). CCH was induced by permanent ligation of the bilateral carotid artery. Open field test

object recognition test and Morris water maze test were used to evaluate exploratory behavior and learning and memorial function at 4 and 12 weeks after the operation for each group of rats. Then double immunofluorescence labeling was used to observe the co-expression of aquaporin-4 (AQP4) in astrocytic endfeet and vascular basement membrane of collagen Ⅳ in the hippocampus. Furthermore

transmission electron microscopy was used to observe the ultrastructure of neurovascular unit in the hippocampus.

Results

Compared with the control group

in CCH groups in 4 and 12 weeks after the operation

① the object discrimination index was decreased clearly (0.86± 0.14

0.71±0.16

0.05; 0.83±0.19

0.64±0.10

0.05)

the escape latencies of place navigation test and spatial probe test were prolonged notably (

0.05); ② the expression of AQP4 in astrocytic endfeet (1.94±0.80

1.10±0.41

0.05; 2.05±0.51

0.96±0.50

0.01)

that of collagen Ⅳ in vascular basement membrane (6.90±2.42

4.25±1.01

0.05; 6.63±2.20

3.66±1.22

0.01)

and the co-expression ratio of them (0.94±0.02

0.91±0.01

0.01; 0.91±0.01

0.89±0.01

0.01) were all decreased obviously; ③ the ultrastructure of neurovascular unit displayed that astrocytic endfeet were separated from the vascular basement membrane

and gliovascular interface and neurovascular unit was damaged in the hippocampus.

Conclusion

CCH facilitates the lasting learning and memory impairment

which may be associated with neurovascular unit dysfunction.

关键词

Keywords

references

SIMARD M ARCUINO G TAKANO T Signaling at the gliovascular interface J Neurosci 2003 23 27 9254 9262 10.1523/JNEUROSCI.23-27-09254.2003 SIMARD M, ARCUINO G, TAKANO T, et al . Signaling at the gliovascular interface[J ] . J Neurosci, 2003, 23(27):9254-9262.

NAGELHUS E A OTTERSEN O P Physiological roles of aquaporin-4 in brain Physiol Rev 2013 93 4 1543 1562 10.1152/physrev.00011.2013 NAGELHUS E A, OTTERSEN O P. Physiological roles of aquaporin-4 in brain[J]. Physiol Rev, 2013, 93(4): 1543-1562. DOI:10.1152/physrev.00011.2013.

ZHAO Z NELSON A R BETSHOLTZ C Establishment and dysfunction of the blood-brain barrier Cell 2015 163 5 1064 1078 10.1016/j.cell.2015.10.067 ZHAO Z, NELSON A R, BETSHOLTZ C, et al . Establishment and dysfunction of the blood-brain barrier[J ] . Cell, 2015, 163(5): 1064-1078. DOI:10.1016/j.cell.2015.10.067.

KISLER K NELSON A R MONTAGNE A Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease Nat Rev Neurosci 2017 18 7 419 434 10.1038/nrn.2017.48 KISLER K, NELSON A R, MONTAGNE A, et al . Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease[J ] . Nat Rev Neurosci, 2017, 18(7): 419-434. DOI:10.1038/nrn.2017.48.

ZHAO Y GONG C X From chronic cerebral hypoperfusion to Alzheimer-like brain pathology and neurodegeneration Cell Mol Neurobiol 2015 35 1 101 110 10.1007/s10571-014-0127-9 ZHAO Y, GONG C X. From chronic cerebral hypoperfusion to Alzheimer-like brain pathology and neurodegeneration[J]. Cell Mol Neurobiol, 2015, 35(1): 101-110. DOI:10.1007/s10571-014-0127-9.

O'BRIEN J T THOMAS A Vascular dementia Lancet 2015 386 10004 1698 1706 10.1016/S0140-6736(15)00463-8 O'BRIEN J T, THOMAS A. Vascular dementia[J]. Lancet, 2015, 386(10004): 1698-1706. DOI:10.1016/S0140- 6736(15)00463-8.

FARKAS E LUITEN P G BARI F Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases Brain Res Rev 2007 54 1 162 180 10.1016/j.brainresrev.2007.01.003 FARKAS E, LUITEN P G, BARI F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases[J]. Brain Res Rev, 2007, 54(1): 162-180. DOI:10.1016/j.brainresrev.2007.01.003.

DU S Q WANG X R XIAO L Y Molecular mechanisms of vascular dementia: what can be learned from animal models of chronic cerebral hypoperfusion Mol Neurobiol 2017 54 5 3670 3682 10.1007/s12035-016-9915-1 DU S Q, WANG X R, XIAO L Y, et al . Molecular mechanisms of vascular dementia: what can be learned from animal models of chronic cerebral hypoperfusion[J ] . Mol Neurobiol, 2017, 54(5):3670-3682.DOI:10.1007/s12035-016-9915-1.

WANG Z FAN J WANG J Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silent synapses increase in rats Behav Brain Res 2016 301 243 252 10.1016/j.bbr.2015.12.047 WANG Z, FAN J, WANG J, et al . Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term h ippocampal silent synapses increase in rats[J ] . Behav Brain Res, 2016, 301: 243-252. DOI:10.1016/j.bbr.2015.12.047.

DUNCOMBE J LENNEN R J JANSEN M A Ageing causes prominent neurovascular dysfunction associated with loss of astrocytic contacts and gliosis Neuropathol Appl Neurobiol 2017 43 6 477 491 10.1111/nan.12375 DUNCOMBE J, LENNEN R J, JANSEN M A, et al . Ageing causes prominent neurovascular dysfunction associated with loss of astrocytic contacts and gliosis[J ] . Neuropathol Appl Neurobiol, 2017, 43(6): 477-491. DOI:10.1111/nan.12375.

JIAN H YI-FANG W QI L Cerebral blood flow and metabolic changes in hippocampal regions of a modified rat model with chronic cerebral hypoperfusion Acta Neurol Belg 2013 113 3 313 317 10.1007/s13760-012-0154-6 JIAN H, YI-FANG W, QI L, et al . Cerebral blood flow and metabolic changes in hippocampal regions of a modified rat model with chronic cerebral hypoperfusion[J ] . Acta Neurol Belg, 2013, 113(3): 313-317. DOI:10.1007/s13760-012-0154-6.

WANG L DU Y WANG K Chronic cerebral hypoperfusion induces memory deficits and facilitates Aβ generation in C57BL/6J mice Exp Neurol 2016 283 Pt A 353 364 10.1016/j.expneurol.2016.07.006 WANG L, DU Y, WANG K, et al . Chronic cerebral hypoperfusion induces memory deficits and facilitates Aβ generation in C57BL/6J mice[J ] . Exp Neurol, 2016, 283(Pt A): 353-364. DOI:10.1016/j.expneurol.2016.07.006.

THOMSEN M S ROUTHE L J MOOS T The vascular basement membrane in the healthy and pathological brain J Cereb Blood Flow Metab 2017 37 10 3300 3317 10.1177/0271678X17722436 THOMSEN M S, ROUTHE L J, MOOS T. The vascular basement membrane in the healthy and pathological brain[J]. J Cereb Blood Flow Metab, 2017, 37(10): 3300-3317. DOI:10.1177/0271678X17722436.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Exogenous carbon monoxide improves postoperative anxiety-like behaviors in elderly rats by inhibiting excessive autophagy of astrocytes

Tetramethylpyrazine protects rat astrocytes against H₂O₂-induced oxidative stress injury

Sulforaphane inhibits astrocyte proliferation by induced LPS in mice

Sympathetic denervation impairs cerebral arteriogenesis after chronic cerebral hypoperfusion in rats

Characteristics of oligodendrocyte precursor cells in cuprizone-induced demyelination models

Related Author

Shujuan LIANG

Dongxue ZHANG

Limin ZHANG

Huitao MIAO

Zhiyou WU

Weichao ZHENG

Yue XIN

Jiexia WANG

Related Institution

Graduate School of Hebei North University

Graduate School of Hebei Medical University

Department of Anesthesiology, Cangzhou Central Hospital

Department of Gerontology, Cangzhou Central Hospital

Department of Anesthesiology, First Hospital of Qinhuangdao

⁰