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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2014-05-01
|
| Series: | Journal of Inflammation Research |
| Online Access: | http://www.dovepress.com/prostacyclin-mediates-endothelial-cox-2-dependent-neuroprotective-effe-a16933 |
| _version_ | 1818904741896257536 |
|---|---|
| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-19T21:12:16Z |
| format | Article |
| id | doaj.art-20790bcd7c7444f6badbda51952ccf7a |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-12-19T21:12:16Z |
| publishDate | 2014-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-20790bcd7c7444f6badbda51952ccf7a2022-12-21T20:05:27ZengDove Medical PressJournal of Inflammation Research1178-70312014-05-012014default576716933Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injuryAn YBelevych NWang YZhang HNasse JSHerschman HChen QTarr ALiu XQuan NYing 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, PGI2http://www.dovepress.com/prostacyclin-mediates-endothelial-cox-2-dependent-neuroprotective-effe-a16933 |
| spellingShingle | 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 Journal of Inflammation Research |
| title | 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_short | 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 |
| url | http://www.dovepress.com/prostacyclin-mediates-endothelial-cox-2-dependent-neuroprotective-effe-a16933 |
| work_keys_str_mv | AT any prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT belevychn prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT wangy prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT zhangh prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT nassejs prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT herschmanh prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT chenq prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT tarra prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT liux prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury AT quann prostacyclinmediatesendothelialcox2dependentneuroprotectiveeffectsduringexcitotoxicbraininjury |