title: Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury.
abstract: 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-2(flox/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.
authors: Institute for Behavior Medicine Research, Columbus, OH, USA ; Department of Oral Biology, College of Dentistry, Columbus, OH, USA.
authors: Ying
authors: Y
authors: An
authors: Institute for Behavior Medicine Research, Columbus, OH, USA ; Department of Oral Biology, College of Dentistry, Columbus, OH, USA.
authors: Natalya
authors: N
authors: Belevych
authors: Institute for Behavior Medicine Research, Columbus, OH, USA ; Department of Oral Biology, College of Dentistry, Columbus, OH, USA.
authors: Yufen
authors: Y
authors: Wang
authors: Institute for Behavior Medicine Research, Columbus, OH, USA.
authors: Hao
authors: H
authors: Zhang
authors: Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH, USA.
authors: Jason S
authors: JS
authors: Nasse
authors: Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA.
authors: Harvey
authors: H
authors: Herschman
authors: Institute for Behavior Medicine Research, Columbus, OH, USA ; Department of Oral Biology, College of Dentistry, Columbus, OH, USA.
authors: Qun
authors: Q
authors: Chen
authors: Institute for Behavior Medicine Research, Columbus, OH, USA ; Department of Oral Biology, College of Dentistry, Columbus, OH, USA.
authors: Andrew
authors: A
authors: Tarr
authors: Institute for Behavior Medicine Research, Columbus, OH, USA ; Department of Oral Biology, College of Dentistry, Columbus, OH, USA.
authors: Xiaoyu
authors: X
authors: Liu
authors: Institute for Behavior Medicine Research, Columbus, OH, USA ; Department of Oral Biology, College of Dentistry, Columbus, OH, USA.
authors: Ning
authors: N
authors: Quan
keywords: PGI2; conditional COX-2 deletion; neural injury; neutrophil; prostaglandins