Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia.
We have characterized the induction of the mitogen-inducible form of cyclo-oxygenase, COX-2, during focal cerebral ischemia following permanent middle cerebral artery occlusion (MCAO) in the rat. Marked unilateral induction of COX-2 mRNA was detected in ischemic regions ipsilateral to the occlusion. A significant increase in COX-2 mRNA was detected in "core" and "penumbra" regions of the cerebral cortex between 4 and 24 h after occlusion; this was most marked at 4 h in the penumbra region, in which a 19-fold increase above untreated control levels was detected. A smaller but significant induction was also detected at 4 h in the caudate. A correlation was demonstrated between the extent of COX-2 mRNA induction in cortical regions at 4 h and the severity of tissue damage subsequently detected at 24 h post MCAO. MK-801 significantly attenuated the induction of COX-2 mRNA in the penumbra region at 4 h. The demonstration of COX-2 induction following experimental ischemia highlights the importance of this reaction and its products and by-products, for example, free radicals, in the tissue response to this insult.
Department of Biochemistry, Charing Cross and Westminster Medical School, London, England.
Y
Y
Collaço-Moraes
B
B
Aspey
M
M
Harrison
J
J
de Belleroche
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D051546:Cyclooxygenase 2; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016291:Dizocilpine Maleate; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases