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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

TitleEndothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet
Authors
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
Citation
Journal Of Cerebral Blood Flow And Metabolism, 2005, v. 25 n. 8, p. 998-1011 How to Cite?
Abstract
Stroke 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.
Persistent Identifierhttp://hdl.handle.net/10722/87998
ISSN
2013 Impact Factor: 5.339
2013 SCImago Journal Rankings: 2.823
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLo, ACYen_HK
dc.contributor.authorChen, AYSen_HK
dc.contributor.authorHung, VKLen_HK
dc.contributor.authorYaw, LPen_HK
dc.contributor.authorFung, MKLen_HK
dc.contributor.authorHo, MCYen_HK
dc.contributor.authorTsang, MCSen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorChung, SKen_HK
dc.date.accessioned2010-09-06T09:37:19Z-
dc.date.available2010-09-06T09:37:19Z-
dc.date.issued2005en_HK
dc.identifier.citationJournal Of Cerebral Blood Flow And Metabolism, 2005, v. 25 n. 8, p. 998-1011en_HK
dc.identifier.issn0271-678Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/87998-
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.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jcbfmen_HK
dc.relation.ispartofJournal of Cerebral Blood Flow and Metabolismen_HK
dc.subjectCerebral infarcten_HK
dc.subjectEndothelin receptor antagonisten_HK
dc.subjectHypoxia/ischemiaen_HK
dc.subjectNeurologic deficiten_HK
dc.subjectStrokeen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAquaporin 4en_HK
dc.subject.meshAquaporins - biosynthesisen_HK
dc.subject.meshAstrocytes - metabolism - ultrastructureen_HK
dc.subject.meshBlood Pressure - physiologyen_HK
dc.subject.meshBlood-Brain Barrier - physiologyen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshBrain - pathologyen_HK
dc.subject.meshBrain Edema - etiology - metabolismen_HK
dc.subject.meshColoring Agentsen_HK
dc.subject.meshEndothelin-1 - biosynthesisen_HK
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_HK
dc.subject.meshEvans Blueen_HK
dc.subject.meshGlial Fibrillary Acidic Protein - genetics - metabolismen_HK
dc.subject.meshIn Situ Hybridizationen_HK
dc.subject.meshInfarction, Middle Cerebral Artery - complications - metabolism - pathologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Transgenicen_HK
dc.subject.meshNervous System Diseases - etiologyen_HK
dc.subject.meshReceptor, Endothelin A - antagonists & inhibitorsen_HK
dc.subject.meshReceptor, Endothelin B - antagonists & inhibitorsen_HK
dc.subject.meshReperfusion Injury - metabolism - pathologyen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshWater - metabolismen_HK
dc.titleEndothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feeten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0271-678X&volume=25&spage=998&epage=1011&date=2005&atitle=Endothelin-1+overexpression+leads+to+further+water+accumulation+and+brain+edema+after+middle+cerebral+artery+occlusion+via+aquaporin+4+expression+in+astrocytic+end-feeten_HK
dc.identifier.emailLo, ACY: amylo@hkucc.hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.authorityLo, ACY=rp00425en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.jcbfm.9600108en_HK
dc.identifier.pmid15815585en_HK
dc.identifier.scopuseid_2-s2.0-23044459474en_HK
dc.identifier.hkuros106113en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-23044459474&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue8en_HK
dc.identifier.spage998en_HK
dc.identifier.epage1011en_HK
dc.identifier.isiWOS:000230877600007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLo, ACY=7102780640en_HK
dc.identifier.scopusauthoridChen, AYS=8718040100en_HK
dc.identifier.scopusauthoridHung, VKL=55112576200en_HK
dc.identifier.scopusauthoridYaw, LP=6507725513en_HK
dc.identifier.scopusauthoridFung, MKL=8718040400en_HK
dc.identifier.scopusauthoridHo, MCY=7403080620en_HK
dc.identifier.scopusauthoridTsang, MCS=9239694300en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK

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