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

被引:134
作者
Kunz, T [1 ]
Oliw, EH [1 ]
机构
[1] Uppsala Univ, Uppsala Biomed Ctr, Dept Pharmaceut Biosci, SE-75124 Uppsala, Sweden
关键词
limbic neuroprotection; nonsteroidal anti-inflammatory drugs; seizure; TUNEL staining;
D O I
10.1046/j.1460-9568.2001.01420.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Treatment of male Sprague-Dawley rats with kainic acid (10 mg/kg, i.p.) triggered limbic seizures in 60% of the animals starting within 30 min and lasting for about 6 h. Cyclooxygenase-2 (COX-2) mRNA was strongly induced in the pyramidal cells of the hippocampus, in the amygdala and the piriform cortex after 8 h, as shown by in situ hybridization, and returned to control levels after 72 h. At this time marked cell loss occurred in the CA1-CA3 areas of the hippocampus. We hypothesize that rofecoxib, a selective COX-2 inhibitor, might abbreviate the late neurotoxicity, possibly associated with COX-2 induction. Animals which developed seizures were treated for 3 days with rofecoxib (10 mg/kg, i.p., n = 12) starting 6 or 8 h after kainic acid injection. Histological staining of viable cells confirmed that rofecoxib treatment selectively diminished cell loss in the hippocampus. The TdT-mediated dUTP nick end labelling (TUNEL) technique was used to estimate delayed cell 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. Treatment with rofecoxib selectively and significantly (P < 0.05) attenuated the number of TUNEL-positive cells in the hippocampus, whereas the cells of the thalamus, amygdala and piriform cortex were not protected. Therefore we conclude that COX-2 might contribute to cell death of pyramidal cells of the hippocampus as a consequence of limbic seizures.
引用
收藏
页码:569 / 575
页数:7
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