Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats

Background Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression ofischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focalcerebral ischemia/reperfusion injury in rats.Methods Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group,ischemia/reperfusion (l/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenouslyvia the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficitscores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains wereremoved and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with2,3,5-triphenyltetrazolium chloride (TTC) staining.Results The rats in the l/R group had lower NDSs (P<0.05), larger infarct volume (P<0.05), lower HMGB1 levels (P<0.05), and higher TNF-α levels (P<0.05) compared with those in the sham group. Parecoxib administration significantlyimproved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P<0.05).Conclusions Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with theattenuation of inflammatory reaction and the inhibition of inflammatory mediators.