Stroke. 2005;36:182-185
Published online before print January 6, 2005, doi: 10.1161/01.STR.0000153797.33611.d8
Published online before print January 6, 2005, doi: 10.1161/01.STR.0000153797.33611.d8
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(Stroke. 2005;36:182.)
© 2005 American Heart Association, Inc.
Advances in Stroke 2004 |
The Janus Face of Cyclooxygenase-2 in Ischemic Stroke
Shifting Toward Downstream Targets
From the Division of Neurobiology, Department of Neurology and Neuroscience (C.I.), Weill Medical College of Cornell University, New York, NY; and the Department of Neurology and Rehabilitation (P.B.G.), University of Illinois College of Medicine.
Correspondence to Dr C. Iadecola, Division of Neurobiology, Weill Medical College of Cornell University, 411 E 69th St, KB410, New York, NY 10021. E-mail coi2001@med.cornell.edu
Key Words: Advances in Stroke • cyclooxygenase 2 • anti-inflammatory agents, non-steroidal • stroke, ischemic
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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The rate-limiting enzyme for prostanoid synthesis cyclooxygenase-2 (COX-2) has been implicated in the basic mechanisms of several brain diseases, including stroke, multiple sclerosis and neurodegenerative diseases.1 The approval by the Food and Drug Administration (FDA) of highly selective COX-2 inhibitors for the treatment of pain and rheumatoid arthritis (RA) raised the possibility that these agents could also be used in the treatment of neurological diseases including stroke. However, the occurrence of serious cardiovascular complications in patients receiving COX-2 inhibitors has led to the recent withdrawal from the market of a popular COX-2 inhibitor and has called for a re-evaluation of the therapeutic potential of these drugs. In this article, we briefly review the role of COX-2 in ischemic brain injury and re-examine the validity of the COX-2 pathway as a therapeutic target for ischemic stroke.
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From Arachidonic Acid to Prostanoids: COX, Isomerases, and Prostanoid Receptors |
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COX enzymes catalyze the conversion of arachidonic acid into prostaglandin H2 (PGH2; Figure).2 Arachidonic acid, produced by the breakdown of membrane phospholipids, is metabolized by COX into PGH2 in a 2-step reaction in which the free radical superoxide is also produced.2 Three isoforms of COX have been described. COX-1 is present in most cells and is involved in normal cellular physiology, such as gastric secretion and platelet function.2 COX-2 is expressed constitutively in some organs, such as brain, but is markedly upregulated by a wide variety of stimuli, most notably inflammatory mediators.2 COX-3, a splice variant of COX-1, is highly sensitive to inhibition by acetaminophen and is most abundant in heart and brain.3
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