The selective cyclooxygenase-2 inhibitor rofecoxib reduces kainate-inducedcell death in the rat hippocampus

Treatment of male Sprague-Dawley rats with kainic acid (10 mg/kg, i.p.) tri ggered limbic seizures in 60% of the animals starting within 30 min and las ting for about 6 h. Cyclooxygenase-2 (COX-2) mRNA was strongly induced in t he pyramidal cells of the hippocampus, in the amygdala and the piriform cor tex after 8 h, as shown by in situ hybridization, and returned to control l evels after 72 h. At this time marked cell loss occurred in the CA1-CA3 are as of the hippocampus. We hypothesize that rofecoxib, a selective COX-2 inh ibitor, might abbreviate the late neurotoxicity, possibly associated with C OX-2 induction. Animals which developed seizures were treated for 3 days wi th rofecoxib (10 mg/kg, i.p., n = 12) starting 6 or 8 h after kainic acid i njection. Histological staining of viable cells confirmed that rofecoxib tr eatment selectively diminished cell loss in the hippocampus. The TdT-mediat ed dUTP nick end labelling (TUNEL) technique was used to estimate delayed c ell death. Abundant TUNEL-positive cells were detected in seizure rats 72 h after kainic acid injection in pyramidal cells of the hippocampus (CA1-CA3 ), in cells of the thalamus, the amygdala and the piriform cortex. Treatmen t with rofecoxib selectively and significantly (P < 0.05) attenuated the nu mber of TUNEL-positive cells in the hippocampus, whereas the cells of the t halamus, amygdala and piriform cortex were not protected. Therefore we conc lude that COX-2 might contribute to cell death of pyramidal cells of the hi ppocampus as a consequence of limbic seizures.