Original Article
Journal of Cerebral Blood Flow & Metabolism (2009) 29, 66–72; doi:10.1038/jcbfm.2008.88; published online 23 July 2008
The neuroprotective effect of prostaglandin E2 EP1 receptor inhibition has a wide therapeutic window, is sustained in time and is not sexually dimorphic
This study was supported by NIH Grant NS35806.
Takato Abe1, Alexander Kunz1, Munehisa Shimamura1, Ping Zhou1, Josef Anrather1 and Costantino Iadecola1
1Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York, USA
Correspondence: Dr C Iadecola, Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 411 East 69th Street, KB-410, New York, NY 10021, USA. E-mail: coi2001@med.cornell.edu
Received 31 May 2008; Revised 1 July 2008; Accepted 2 July 2008; Published online 23 July 2008.
Abstract
We investigated the preclinical characteristics of the neuroprotective effect of the prostaglandin E2 type 1 receptor (EP1) antagonist SC51089 in models of focal cerebral ischemia produced by occlusion of the mouse middle cerebral artery (MCA). We found that systemic administration of SC51089 (5 to 20
g/kg; i.p.) reduces the brain injury produced by transient (-50%
8%; n=12; P<0.05) or permanent (-39%
7%; n=12; P<0.05) MCA occlusion. SC51089 was effective even when administered up to 12 h after ischemia. The protective effect was observed both in male and female mice and was sustained for at least 2 weeks after induction of ischemia. The reduction in injury volume was associated with an improvement in neurological function assessed by the Bederson deficit score, the hanging wire test and the corner test. The data provide proof of principle that EP1 receptor inhibition is a potentially valuable strategy for neuroprotection that deserves further preclinical investigation for therapeutic application in human stroke.
Keywords:
SC51089, prostanoids, cyclooxygenase, corner test, middle cerebral artery occlusion
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Relation of Apparent Diffusion Coefficient Changes and Metabolic Disturbances After 1 Hour of Focal Cerebral Ischemia and at Different Reperfusion Phases in RatsJournal of Cerebral Blood Flow & Metabolism Original Article
Cerebellar autoregulation dynamics in humansJournal of Cerebral Blood Flow & Metabolism Original Article
Reduced cerebral fluoro- L -dopamine uptake in adult patients suffering from phenylketonuriaJournal of Cerebral Blood Flow & Metabolism Original Article
Amyloid &bgr; Peptide?Induced Cerebral Endothelial Cell Death Involves Mitochondrial Dysfunction and Caspase ActivationJournal of Cerebral Blood Flow & Metabolism Original Article
See all 64 matches for Research
