CYCLO-OXYGENASE-2 MESSENGER-RNA INDUCTION IN FOCAL CEREBRAL-ISCHEMIA

We have characterized the induction of the mitogen-inducible form of c yclo-oxygenase, COX-2, during focal cerebral ischemia following perman ent middle cerebral artery occlusion (MCAO) in the rat. Marked unilate ral induction of COX-2 mRNA was detected in ischemic regions ipsilater al 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 wa s detected. A smaller but significant induction was also detected at 4 h in the caudate. A correlation was demonstrated between the extent o f 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 signific antly attenuated the induction of COX-2 mRNA in the penumbra region at 4 h. The demonstration of COX-2 induction following experimental isch emia highlights the importance of this reaction and its products and b y-products, for example, free radicals, in the tissue response to this insult.