Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets
| Autor: | James V. Perciaccante, Ferenc Domoki, Ferenc Bari, Michelle Puskar, David W. Busija |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
N-Methylaspartate Swine Indomethacin Ischemia Blood Pressure Pharmacology Hypoxia ischemia chemistry.chemical_compound medicine Excitatory Amino Acid Agonists Animals Cyclooxygenase Inhibitors Neurotransmitter Nitrobenzenes chemistry.chemical_classification Neurons Reactive oxygen species Sulfonamides biology Cyclooxygenase 2 Inhibitors business.industry General Neuroscience Hypoxia (medical) medicine.disease Isoenzymes Thromboxane B2 Vasodilation nervous system chemistry Animals Newborn Enzyme inhibitor Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Cerebrovascular Circulation Hypoxia-Ischemia Brain cardiovascular system biology.protein NMDA receptor Pia Mater Female Cyclooxygenase medicine.symptom business Neuroscience circulatory and respiratory physiology |
| Zdroj: | Neuroreport. 12(18) |
| ISSN: | 0959-4965 |
| Popis: | 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 micromol/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 micromol/l NMDA, mean +/- s.e.m.) of the pre-ischemic response in vehicle animals (p0.05). 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 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. |
| Databáze: | OpenAIRE |
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