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Article: Endothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet
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TitleEndothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet
 
AuthorsLo, ACY
Chen, AYS
Hung, VKL
Yaw, LP
Fung, MKL
Ho, MCY
Tsang, MCS
Chung, SSM
Chung, SK1
 
KeywordsCerebral infarct
Endothelin receptor antagonist
Hypoxia/ischemia
Neurologic deficit
Stroke
 
Issue Date2005
 
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jcbfm
 
CitationJournal Of Cerebral Blood Flow And Metabolism, 2005, v. 25 n. 8, p. 998-1011 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.jcbfm.9600108
 
AbstractStroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ET A antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury. © 2005 ISCBFM. All rights reserved.
 
ISSN0271-678X
2013 Impact Factor: 5.339
2013 SCImago Journal Rankings: 2.823
 
DOIhttp://dx.doi.org/10.1038/sj.jcbfm.9600108
 
ISI Accession Number IDWOS:000230877600007
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLo, ACY
 
dc.contributor.authorChen, AYS
 
dc.contributor.authorHung, VKL
 
dc.contributor.authorYaw, LP
 
dc.contributor.authorFung, MKL
 
dc.contributor.authorHo, MCY
 
dc.contributor.authorTsang, MCS
 
dc.contributor.authorChung, SSM
 
dc.contributor.authorChung, SK
 
dc.date.accessioned2010-09-06T09:37:19Z
 
dc.date.available2010-09-06T09:37:19Z
 
dc.date.issued2005
 
dc.description.abstractStroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ET A antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury. © 2005 ISCBFM. All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Cerebral Blood Flow And Metabolism, 2005, v. 25 n. 8, p. 998-1011 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.jcbfm.9600108
 
dc.identifier.doihttp://dx.doi.org/10.1038/sj.jcbfm.9600108
 
dc.identifier.epage1011
 
dc.identifier.hkuros106113
 
dc.identifier.isiWOS:000230877600007
 
dc.identifier.issn0271-678X
2013 Impact Factor: 5.339
2013 SCImago Journal Rankings: 2.823
 
dc.identifier.issue8
 
dc.identifier.openurl
 
dc.identifier.pmid15815585
 
dc.identifier.scopuseid_2-s2.0-23044459474
 
dc.identifier.spage998
 
dc.identifier.urihttp://hdl.handle.net/10722/87998
 
dc.identifier.volume25
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jcbfm
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Cerebral Blood Flow and Metabolism
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAnimals
 
dc.subject.meshAquaporin 4
 
dc.subject.meshAquaporins - biosynthesis
 
dc.subject.meshAstrocytes - metabolism - ultrastructure
 
dc.subject.meshBlood Pressure - physiology
 
dc.subject.meshBlood-Brain Barrier - physiology
 
dc.subject.meshBlotting, Western
 
dc.subject.meshBrain - pathology
 
dc.subject.meshBrain Edema - etiology - metabolism
 
dc.subject.meshColoring Agents
 
dc.subject.meshEndothelin-1 - biosynthesis
 
dc.subject.meshEnzyme-Linked Immunosorbent Assay
 
dc.subject.meshEvans Blue
 
dc.subject.meshGlial Fibrillary Acidic Protein - genetics - metabolism
 
dc.subject.meshIn Situ Hybridization
 
dc.subject.meshInfarction, Middle Cerebral Artery - complications - metabolism - pathology
 
dc.subject.meshMice
 
dc.subject.meshMice, Transgenic
 
dc.subject.meshNervous System Diseases - etiology
 
dc.subject.meshReceptor, Endothelin A - antagonists & inhibitors
 
dc.subject.meshReceptor, Endothelin B - antagonists & inhibitors
 
dc.subject.meshReperfusion Injury - metabolism - pathology
 
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
 
dc.subject.meshWater - metabolism
 
dc.subjectCerebral infarct
 
dc.subjectEndothelin receptor antagonist
 
dc.subjectHypoxia/ischemia
 
dc.subjectNeurologic deficit
 
dc.subjectStroke
 
dc.titleEndothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong