title: Inhibition of cyclooxygenase 2 by nimesulide decreases prostaglandin E2 formation but does not alter brain edema or clinical recovery after closed head injury in rats.
abstract: Recently, the enzyme cyclooxygenase (COX) has been recognized to exist as constitutive (COX-1) and inducible isoforms (COX-2). In previous studies, drugs that were inhibitors of both COX-1 and COX-2 failed to decrease brain edema formation or improve Neurological Severity Score (NSS) after closed head trauma (CHT), although some did decrease prostaglandin-E2 (PGE2) formation. The present study examined whether or not a specific inhibitor of COX-2 (nimesulide) exerts a beneficial effect after CHT in rats. Halothane-anesthetized rats (n = 8 in each group) were randomly assigned to one of four groups: surgery, no CHT, no drug (group 1); surgery, no CHT, nimesulide 30 mg/kg intraperitoneally (IP) (group 2); surgery, CHT, no drug (group 3); and surgery, CHT, nimesulide 30 mg/kg IP (group 4). NSS was determined at 1 and 24 h, and brain tissue PGE2 concentration and water content were determined after killing at 24 h. Treatment with nimesulide did not improve NSS (NSS at 24 h = 11+/-6 [median +/- range] in group 3 and 12+/-4 in group 4) or edema formation (brain water content at 24 h = 84.3+/-1.8% [mean +/- SD] in group 3 and 83.8+/-1.9% in group 4). However, nimesulide did decrease cortical and hypothalamic PGE2 formation by 41% and 47%, respectively during the first hour of incubation after brain tissue sampling. The authors conclude that although nimesulide does reduce tissue PGE2 formation, it does not exert a beneficial effect on brain tissue edema or functional activity after CHT in rats.
authors.affiliation: Division of Anesthesiology, Soroka Medical Center, Faculty of Health Science, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Koyfman
authors.forename: J
authors.initials: J
authors.lastname: Kaplanski
authors.forename: A A
authors.initials: AA
authors.lastname: Artru
authors.forename: D
authors.initials: D
authors.lastname: Talmor
authors.forename: M
authors.initials: M
authors.lastname: Rubin
authors.forename: Y
authors.initials: Y
authors.lastname: Shapira
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D001834:Body Water / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015232:Dinoprostone / Q000032:analysis / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006221:Halothane / Q000008:administration & dosage; D016489:Head Injuries, Closed / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000494:pharmacology*; D009460:Neurologic Examination; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018685:Anesthetics, Inhalation; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D006221:Halothane; C012655:nimesulide