Transgenic mice over-expressing endothelial endothelin-1 show cognitive deficit with blood-brain barrier breakdown after transient ischemia with long-term reperfusion

doi:10.1016/j.nlm.2013.01.002

科研成果详情

题名	Transgenic mice over-expressing endothelial endothelin-1 show cognitive deficit with blood-brain barrier breakdown after transient ischemia with long-term reperfusion
作者	Zhang，Xu 1; Yeung，Patrick K.K.1; McAlonan，Grainne M.3; Chung，Stephen S.M.4; Chung，Sookja K.1,2
发表日期	2013
发表期刊	Neurobiology of Learning and Memory
ISSN/eISSN	1074-7427
卷号	101 页码:46-54
摘要	Increased 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.
关键词	Anxiety BBB breakdown Cognitive deficit Endothelin-1 transgenic mice Ischemia/reperfusion brain injury
DOI	10.1016/j.nlm.2013.01.002
URL	查看来源
语种	英语English
Scopus入藏号	2-s2.0-84873274538
引用统计	被引频次：46[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://repository.uic.edu.cn/handle/39GCC9TT/6552
专题	北师香港浸会大学
作者单位	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
推荐引用方式 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.