Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

Ying An,1,2 Natalya Belevych,1,2 Yufen Wang,1,2 Hao Zhang,1 Jason S Nasse,3 Harvey Herschman,4 Qun Chen,1,2 Andrew Tarr,1,2 Xiaoyu Liu,1,2 Ning Quan1,21Institute for Behavior Medicine Research, 2Department of Oral Biology, College of Dentistry, 3Neuroscience Graduate Studies Program, The Ohio State...

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Autores principales: An Y, Belevych N, Wang Y, Zhang H, Nasse JS, Herschman H, Chen Q, Tarr A, Liu X, Quan N
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2014
Materias:
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Acceso en línea:https://doaj.org/article/20790bcd7c7444f6badbda51952ccf7a
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spelling oai:doaj.org-article:20790bcd7c7444f6badbda51952ccf7a2021-12-02T00:51:12ZProstacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury1178-7031https://doaj.org/article/20790bcd7c7444f6badbda51952ccf7a2014-05-01T00:00:00Zhttp://www.dovepress.com/prostacyclin-mediates-endothelial-cox-2-dependent-neuroprotective-effe-a16933https://doaj.org/toc/1178-7031 Ying An,1,2 Natalya Belevych,1,2 Yufen Wang,1,2 Hao Zhang,1 Jason S Nasse,3 Harvey Herschman,4 Qun Chen,1,2 Andrew Tarr,1,2 Xiaoyu Liu,1,2 Ning Quan1,21Institute for Behavior Medicine Research, 2Department of Oral Biology, College of Dentistry, 3Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH, USA; 4Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USAAbstract: In a previous study, we found that intracerebral administration of excitotoxin (RS)-(tetrazole-5yl) glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox). In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2) in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection.Keywords: neural injury, prostaglandins, neutrophil, conditional COX-2 deletion, PGI2An YBelevych NWang YZhang HNasse JSHerschman HChen QTarr ALiu XQuan NDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2014, Iss default, Pp 57-67 (2014)
institution DOAJ
collection DOAJ
language EN
topic Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
An Y
Belevych N
Wang Y
Zhang H
Nasse JS
Herschman H
Chen Q
Tarr A
Liu X
Quan N
Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury
description Ying An,1,2 Natalya Belevych,1,2 Yufen Wang,1,2 Hao Zhang,1 Jason S Nasse,3 Harvey Herschman,4 Qun Chen,1,2 Andrew Tarr,1,2 Xiaoyu Liu,1,2 Ning Quan1,21Institute for Behavior Medicine Research, 2Department of Oral Biology, College of Dentistry, 3Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH, USA; 4Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USAAbstract: In a previous study, we found that intracerebral administration of excitotoxin (RS)-(tetrazole-5yl) glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox). In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2) in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection.Keywords: neural injury, prostaglandins, neutrophil, conditional COX-2 deletion, PGI2
format article
author An Y
Belevych N
Wang Y
Zhang H
Nasse JS
Herschman H
Chen Q
Tarr A
Liu X
Quan N
author_facet An Y
Belevych N
Wang Y
Zhang H
Nasse JS
Herschman H
Chen Q
Tarr A
Liu X
Quan N
author_sort An Y
title Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury
title_short Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury
title_full Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury
title_fullStr Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury
title_full_unstemmed Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury
title_sort prostacyclin mediates endothelial cox-2-dependent neuroprotective effects during excitotoxic brain injury
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/20790bcd7c7444f6badbda51952ccf7a
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AT belevychn prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
AT wangy prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
AT zhangh prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
AT nassejs prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
AT herschmanh prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
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AT tarra prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
AT liux prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
AT quann prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury
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