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Article: Targeted overexpression of endothelin-1 in astrocytes leads to more severe cytotoxic brain edema and higher mortality

TitleTargeted overexpression of endothelin-1 in astrocytes leads to more severe cytotoxic brain edema and higher mortality
Authors
KeywordsAquaporin
Astrocyte
Cytotoxic edema
Endothelin-1
Vasopressin receptor antagonist
Water intoxication
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jcbfm
Citation
Journal Of Cerebral Blood Flow And Metabolism, 2009, v. 29 n. 12, p. 1891-1902 How to Cite?
AbstractTransgenic mice overexpressing endothelin-1 (ET-1) in astrocytes (GET-1) displayed more severe brain edema and neurologic dysfunction after experimental ischemic stroke. However, it was not clear whether astrocytic ET-1 contributed to cytotoxic or vasogenic edema associated with stroke. In this study, the role of astrocytic ET-1 in cytotoxic edema and brain injury was investigated. Upon acute water intoxication, the GET-1 mice had a lower survival rate and more severe neurologic deficits. Such an exacerbated condition in the GET-1 mice may be a result of a significant increase in cerebral water content and increased expression of the water channel protein, aquaporin 4 (AQP-4). The GET-1 mice treated with OPC-31260, a nonpeptide arginine vasopressin V2 receptor antagonist, were alleviated from the cerebral water accumulation and neurologic deficit during the early time period after water intoxication. In addition, a significant reduction of AQP-4 expression was observed in astrocytic end-feet AQP-4 in the hippocampus of the GET-1 mice treated with OPC-31260. Therefore, ET-1-induced AQP-4 expression and cerebral water accumulation are the key factors in brain edema associated with acute water intoxication. The V 2 receptor antagonist, OPC-31260, may be one of the effective drugs for the early treatment of ET-1-induced cytotoxic edema and brain injury. © 2009 ISCBFM All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/124471
ISSN
2015 Impact Factor: 4.929
2015 SCImago Journal Rankings: 3.004
ISI Accession Number ID
Funding AgencyGrant Number
RGC
University Grants Council of Hong KongAoE/B-15/01
Funding Information:

This study was partly supported by the RGC grant to Professor SK Chung and the Area of Excellence from University Grants Council of Hong Kong on 'Molecular Neuroscience: Basic Research and Drug Discovery' (AoE/B-15/01).

References

 

DC FieldValueLanguage
dc.contributor.authorYeung, PKKen_HK
dc.contributor.authorLo, ACYen_HK
dc.contributor.authorLeung, JWCen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorChung, SKen_HK
dc.date.accessioned2010-10-31T10:36:15Z-
dc.date.available2010-10-31T10:36:15Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Cerebral Blood Flow And Metabolism, 2009, v. 29 n. 12, p. 1891-1902en_HK
dc.identifier.issn0271-678Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/124471-
dc.description.abstractTransgenic mice overexpressing endothelin-1 (ET-1) in astrocytes (GET-1) displayed more severe brain edema and neurologic dysfunction after experimental ischemic stroke. However, it was not clear whether astrocytic ET-1 contributed to cytotoxic or vasogenic edema associated with stroke. In this study, the role of astrocytic ET-1 in cytotoxic edema and brain injury was investigated. Upon acute water intoxication, the GET-1 mice had a lower survival rate and more severe neurologic deficits. Such an exacerbated condition in the GET-1 mice may be a result of a significant increase in cerebral water content and increased expression of the water channel protein, aquaporin 4 (AQP-4). The GET-1 mice treated with OPC-31260, a nonpeptide arginine vasopressin V2 receptor antagonist, were alleviated from the cerebral water accumulation and neurologic deficit during the early time period after water intoxication. In addition, a significant reduction of AQP-4 expression was observed in astrocytic end-feet AQP-4 in the hippocampus of the GET-1 mice treated with OPC-31260. Therefore, ET-1-induced AQP-4 expression and cerebral water accumulation are the key factors in brain edema associated with acute water intoxication. The V 2 receptor antagonist, OPC-31260, may be one of the effective drugs for the early treatment of ET-1-induced cytotoxic edema and brain injury. © 2009 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.subjectAquaporinen_HK
dc.subjectAstrocyteen_HK
dc.subjectCytotoxic edemaen_HK
dc.subjectEndothelin-1en_HK
dc.subjectVasopressin receptor antagonisten_HK
dc.subjectWater intoxicationen_HK
dc.subject.meshAquaporin 4 - genetics - metabolism-
dc.subject.meshAstrocytes - metabolism-
dc.subject.meshBrain Edema - chemically induced - physiopathology-
dc.subject.meshEndothelin-1 - genetics - metabolism-
dc.subject.meshUp-Regulation-
dc.titleTargeted overexpression of endothelin-1 in astrocytes leads to more severe cytotoxic brain edema and higher mortalityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0271-678X&volume=29&spage=1891&epage=1902&date=2009&atitle=Targeted+overexpression+of+endothelin-1+in+astrocytes+leads+to+more+severe+cytotoxic+brain+edema+and+higher+mortality-
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/jcbfm.2009.175en_HK
dc.identifier.pmid19707218en_HK
dc.identifier.scopuseid_2-s2.0-72049122125en_HK
dc.identifier.hkuros181688en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-72049122125&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume29en_HK
dc.identifier.issue12en_HK
dc.identifier.spage1891en_HK
dc.identifier.epage1902en_HK
dc.identifier.eissn1559-7016-
dc.identifier.isiWOS:000272182600004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYeung, PKK=35486097200en_HK
dc.identifier.scopusauthoridLo, ACY=7102780640en_HK
dc.identifier.scopusauthoridLeung, JWC=8978634300en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.citeulike8158518-

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