J Koistinaho1, S Koponen, P H Chan. 1. A.I. Virtanen Institute for Molecular Sciences, University of Kuopio Finland. jari.koistinaho@uku.fi
Abstract
BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2) is implicated in ischemic neuronal death. In focal ischemia, its mRNA induction is mediated through N-methyl-D-aspartic acid (NMDA) receptors and phospholipase A(2). Because mechanisms of neuronal death involving COX-2 in global ischemia are unclear, we studied the time course and regulation of COX-2 expression in rat brain global ischemia. METHODS: Global ischemia was induced by a 4-vessel occlusion method. COX-2 mRNA levels were demonstrated with in situ hybridization and COX-2 protein with immunocytochemistry. Several animals were pretreated with MK-801, an NMDA receptor antagonist; 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist; and dexamethasone. RESULTS: In the cortex, the CA3 hippocampal region and dentate gyrus expression of COX-2 mRNA peaked at 4 to 8 hours, while in the CA1 region COX-2 mRNA levels were high at 4 to 24 hours. COX-2 protein was induced in the corresponding regions at 12 to 24 hours, but in the CA1 neurons the protein was still seen at 3 days. COX-2 mRNA induction in the cortex was inhibited by NBQX and dexamethasone and in CA1 neurons was inhibited by NBQX. MK-801 did not suppress COX-2 induction. CONCLUSIONS: COX-2 is differentially induced in the cortex and hippocampal structures after global ischemia. The prolonged COX-2 expression in the vulnerable CA1 neurons is regulated by AMPA receptors, suggesting that COX-2 expression is likely to be associated with AMPA receptor-mediated neuronal death in global ischemia. Glucocorticoids may not be efficiently used to inhibit ischemia-induced COX-2 expression in the hippocampus.
BACKGROUND AND PURPOSE:Cyclooxygenase-2 (COX-2) is implicated in ischemic neuronal death. In focal ischemia, its mRNA induction is mediated through N-methyl-D-aspartic acid (NMDA) receptors and phospholipase A(2). Because mechanisms of neuronal death involving COX-2 in global ischemia are unclear, we studied the time course and regulation of COX-2 expression in rat brain global ischemia. METHODS: Global ischemia was induced by a 4-vessel occlusion method. COX-2 mRNA levels were demonstrated with in situ hybridization and COX-2 protein with immunocytochemistry. Several animals were pretreated with MK-801, an NMDA receptor antagonist; 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist; and dexamethasone. RESULTS: In the cortex, the CA3 hippocampal region and dentate gyrus expression of COX-2 mRNA peaked at 4 to 8 hours, while in the CA1 region COX-2 mRNA levels were high at 4 to 24 hours. COX-2 protein was induced in the corresponding regions at 12 to 24 hours, but in the CA1 neurons the protein was still seen at 3 days. COX-2 mRNA induction in the cortex was inhibited by NBQX and dexamethasone and in CA1 neurons was inhibited by NBQX. MK-801 did not suppress COX-2 induction. CONCLUSIONS:COX-2 is differentially induced in the cortex and hippocampal structures after global ischemia. The prolonged COX-2 expression in the vulnerable CA1 neurons is regulated by AMPA receptors, suggesting that COX-2 expression is likely to be associated with AMPA receptor-mediated neuronal death in global ischemia. Glucocorticoids may not be efficiently used to inhibit ischemia-induced COX-2 expression in the hippocampus.
Authors: Eduardo Candelario-Jalil; Armando González-Falcón; Michel García-Cabrera; Dalia Alvarez; Said Al-Dalain; Gregorio Martínez; Olga Sonia León; Joe E Springer Journal: J Neurochem Date: 2003-08 Impact factor: 5.372
Authors: Tatyana Strekalova; Dmitrii Pavlov; Alexander Trofimov; Daniel C Anthony; Andrei Svistunov; Andrey Proshin; Aleksei Umriukhin; Alexei Lyundup; Klaus-Peter Lesch; Raymond Cespuglio Journal: Int J Mol Sci Date: 2022-02-13 Impact factor: 5.923