Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets

被引:27
作者
Domoki, F
Perciaccante, JV
Puskar, M
Bari, F
Busija, DW
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Ctr Invest Neurosci, Winston Salem, NC 27157 USA
[2] Univ Szeged, Fac Med, Dept Physiol, H-6720 Szeged, Hungary
关键词
indomethacin; NMDA; NS398; pial arterioles; prostaglandin H-synthase;
D O I
10.1097/00001756-200112210-00041
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Anoxic stress attenuates NMDA-induced pial arteriolar dilation via a mechanism involving actions of cyclooxygenase (COX)-derived reactive oxygen species (ROS). We examined whether the selective COX-2 inhibitor NS398 would protect neuronal function after global hypoxia/ischemia (H/I) in piglets. Pial arteriolar responses to NMDA (10-100 mu mol/l) were determined using intravital microscopy in anesthetized piglets before and 1 h after H/I. Study groups received vehicle, 0.3, 1, or 5 mg/kg NS398, or 0.3 mg/kg indomethacin (n = 7, 6, 6, 5 and 8, respectively) i.v. 20 min prior to H/I. H/I reduced NMDA-induced dilation to. 44 +/- 6% (100 mu mol/l NMIDA, mean +/- s.e.m.) of the pre-ischemic response in vehicle animals (p<0.05). However NS398 dose-dependently protected arteriolar dilation to NMIDA (77 +/- 8, 81 +/- 16, and 102 +/- 10% preservation at 0.3, 1 and 5 mg/kg, respectively). Indomethacin caused similar preservation. However, indomethacin but not NS398 reduced serum thromboxane B-2 levels to undetectable values. In conclusion, COX-2 appears to be a major source of ROS in the piglet cerebral cortex after H/I. NeuroReport 12:4065-4068 (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:4065 / 4068
页数:4
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