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

File Download Links for fulltext
(May Require Subscription)
Supplementary
  • Basic View
  • Metadata View
  • XML View
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
2011 Impact Factor: 5.008
2011 SCImago Journal Rankings: 0.485
DOIhttp://dx.doi.org/10.1038/sj.jcbfm.9600108
ISI Accession Number IDWOS:000230877600007
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 5.008
2011 SCImago Journal Rankings: 0.485
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
Author Affiliations
  1. The University of Hong Kong