부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.neulet.2008.04.054 Byline: Jun Li (a), Xibin Liang (b), Qian Wang (b), Richard M. Breyer (c), Louise McCullough (a), Katrin Andreasson (b) Keywords: Stroke; Misoprostol; Prostaglandin; PGE.sub.2; Cerebral ischemia Abstract: Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE.sub.2 receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE.sub.2 EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE.sub.2 EP2 and/or EP4 receptors. Author Affiliation: (a) Departments of Neurology and Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, United States (b) Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States (c) Department of Medicine, Division of Nephrology, Vanderbilt University School of Medicine, S3223 MCN, 1161 21st Ave South, Nashville, TN 37232, United States Article History: Received 14 March 2008; Revised 6 April 2008; Accepted 9 April 2008