期刊
NEUROSCIENCE LETTERS
卷 438, 期 2, 页码 210-215出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2008.04.054
关键词
stroke; misoprostol; prostaglandin; PGE(2); cerebral ischemia
资金
- NIDDK NIH HHS [R01 DK046205, R01 DK037097, DK46205, DK37097] Funding Source: Medline
- NINDS NIH HHS [NS050505, R01 NS050505-03, R01 NS055215, R01 NS045727, R01 NS050505, R01 NS055215-03, NS055215, NS045727] Funding Source: Medline
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(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(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 2 h after MCAO, resulted in significant rescue of infarct volume at 24 and 72 h. 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(2) EP2 and/or EP4 receptors. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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