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TitleTransgenic mice over-expressing endothelial endothelin-1 show cognitive deficit with blood-brain barrier breakdown after transient ischemia with long-term reperfusion
Creator
Date Issued2013
Source PublicationNeurobiology of Learning and Memory
ISSN1074-7427
Volume101Pages:46-54
AbstractIncreased level of endothelin-1 (ET-1), a potent vasoconstrictor, has been found in the cerebral spinal fluid (CSF) of patients with multi-infarction dementia, suggesting a possible rolre of ET-1 in cognitive deficit associated with stroke. Previously, we have reported that synthesis of ET-1 is induced in endothelial cells in hypoxic/ischemic conditions. Transgenic mice over-expressing endothelin-1 in endothelial cells (TET-1) developed systemic hypertension and showed more severe brain damage after transient ischemia. To further understand the significance of endothelial ET-1 in cognitive deficit, we subjected adult TET-1 mice to 30. min middle cerebral artery occlusion (MCAO) with 7. days reperfusion. At baseline, TET-1 mice showed similar locomotor activity, emotion and cognitive function compared to non-transgenic (NTg) mice. However, after 30. min MCAO and 7. days reperfusion, although the sensorimotor function measured by neurological scores was recovered in both genotypes, TET-1 mice showed increased anxiety-like behavior in the open field test and impaired spatial learning and reference memory in the Morris water maze. Parallel with these behavioral changes, TET-1 mice showed more severe brain damage with blood-brain-barrier breakdown (BBB), reactive astrogliosis, increased caspase-3, and increased peroxiredoxin 6 (Prx6) expressions around blood vessels in the ipsilateral hippocampus, compared to that of NTg mice, suggesting that ET-1 over-expression in the endothelial cells leads to more severe BBB breakdown and increased oxidative stress which may resulted in neuronal apoptosis and glial reactivity, which might contribute to the emotional changes and cognitive deficits after short-term ischemia with long-term reperfusion. © 2013 Elsevier Inc.
KeywordAnxiety BBB breakdown Cognitive deficit Endothelin-1 transgenic mice Ischemia/reperfusion brain injury
DOI10.1016/j.nlm.2013.01.002
URLView source
Language英语English
Scopus ID2-s2.0-84873274538
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Cited Times:46[WOS]   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
Identifierhttp://repository.uic.edu.cn/handle/39GCC9TT/6552
CollectionBeijing Normal-Hong Kong Baptist University
Affiliation
1.Department of Anatomy,University of Hong Kong,Pokfulam,Hong Kong
2.Research Centre of Heart Brain, Hormone and Healthy Aging,Li Ka Shing Faculty of Medicine,University of Hong Kong, Hong Kong Special Administrative Region,Hong Kong
3.Department of Forensic and Neurodevelopmental Sciences,Institute of Psychiatry,King's College London,London,United Kingdom
4.Division of Science and Technology,United International College,Zhuhai, Guangdong,China
Recommended Citation
GB/T 7714
Zhang,Xu,Yeung,Patrick K.K.,McAlonan,Grainne M.et al. Transgenic mice over-expressing endothelial endothelin-1 show cognitive deficit with blood-brain barrier breakdown after transient ischemia with long-term reperfusion[J]. Neurobiology of Learning and Memory, 2013, 101: 46-54.
APA Zhang,Xu, Yeung,Patrick K.K., McAlonan,Grainne M., Chung,Stephen S.M., & Chung,Sookja K. (2013). Transgenic mice over-expressing endothelial endothelin-1 show cognitive deficit with blood-brain barrier breakdown after transient ischemia with long-term reperfusion. Neurobiology of Learning and Memory, 101, 46-54.
MLA Zhang,Xu,et al."Transgenic mice over-expressing endothelial endothelin-1 show cognitive deficit with blood-brain barrier breakdown after transient ischemia with long-term reperfusion". Neurobiology of Learning and Memory 101(2013): 46-54.
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