NEUROPHARMACOLOGY AND NEUROTOXICOLOGYCyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in pigletsDomoki, Ferenc1,2; Perciaccante, James V.1; Puskar, Michelle1; Bari, Ferenc2; Busija, David W.1, CAAuthor Information 1Department of Physiology and Pharmacology, Center for Investigative Neuroscience, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1010, USA; 2Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, H-6720, Hungary CACorresponding Author Received 26 September 2001; Accepted 19 October 2001 Neuroreport: December 21st, 2001 - Volume 12 - Issue 18 - p 4065-4068 Buy SDC 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 μmol/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 μmol/l NMDA, mean ± s.e.m.) of the pre-ischemic response in vehicle animals (p < 0.05). However, NS398 dose-dependently protected arteriolar dilation to NMDA (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 B2 levels to undetectable values. In conclusion, COX-2 appears to be a major source of ROS in the piglet cerebral cortex after H/I. © 2001 Lippincott Williams & Wilkins, Inc.