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

Recently, the enzyme cyclooxygenase (COX) has been recognized to exist as c onstitutive (COX-1) and inducible isoforms (COX-2). In previous studies, dr ugs chat were inhibitors of both COX-1 and COX-2 failed to decrease brain e dema formation or improve Neurological Severity Score (NSS) after closed he ad trauma (CHT), although some did decrease prostaglandin-E2 (PGE2) formati on. The present study examined whether or not a specific inhibitor of COX-2 (nimesulide) exerts a beneficial effect after CHT in rats. Halothane-anest hetized rats (n = 8 in each group) were randomly assigned to one of four gr oups: 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 determine d 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 +/- S D] in group 3 and 83.8 +/- 1.9% in group 4). However, nimesulide did decrea se cortical and hypothalamic PGE? formation by 41% and 47%, respectively du ring the first hour of incubation after brain tissue sampling. The authors conclude that although nimesulide does reduce tissue PGE2 formation, it doe s not exert a beneficial effect on brain tissue edema or functional activit y after CHT in rats.