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

Domoki, Ferenc and Perciaccante, J. V. and Puskar, M. and Bari, Ferenc (2001) Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets. NEUROREPORT, 12 (18). pp. 4065-4068. ISSN 0959-4965

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Abstract

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.

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