title: Inducible cyclooxygenase-2 expression after experimental intracerebral hemorrhage.
abstract: Cyclooxygenase-2 (COX-2) is an inducible isoform of cyclooxygenase, which catalyzes the conversion of arachidonic acid to prostaglandins and thromboxane. Recent evidence suggests it has a pathological role in cerebral insults, but its involvement in intracerebral hemorrhage (ICH) is unknown. The present study investigates the temporal and anatomic distribution of COX-2 as well as the effect of the selective COX-2 inhibitor NS-398 on brain edema formation and cerebral blood flow in a rat model of ICH. Immunohistochemistry for COX-2 was performed in control rats and 6 h, as well as 1, 3, 7 and 10 days after the injection of 100 microl autologous blood into the right basal ganglia. Double-labeling immunohistochemistry was used to determine the type of COX-2 immunoreactive microvascular-associated cells. Western blot analysis was used to quantify COX-2 protein. The effect of NS-398 on brain water content, ion concentration and cerebral blood flow were assessed 24 h after ICH. The results demonstrated that COX-2 protein was expressed in control brain tissue and induced significantly in the ipsilateral hemisphere at 6 h, as well as 1 and 3 days after ICH. Increased staining of COX-2 in neurons was observed around the blood clot with a peak at 6 h. COX-2 was induced in endothelial cells, perivascular cells as well as infiltrating leukocytes 1 day after ICH. Brain water and ion contents and cerebral blood flow were unaffected by NS-398 administration. Thus, although COX-2 expression was increased in the ipsilateral hemisphere after an autologous blood injection, its products do not appear to be major regulators of blood flow or edema formation following ICH.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA. chaog@umich.edu
authors.forename: C
authors.initials: C
authors.lastname: Gong
authors.forename: S R
authors.initials: SR
authors.lastname: Ennis
authors.forename: J T
authors.initials: JT
authors.lastname: Hoff
authors.forename: R F
authors.initials: RF
authors.lastname: Keep
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases