Nakayama M, Uchimura K, Zhu R L, Nagayama T, Rose M E, Stetler R A, Isakson P C, Chen J, Graham S H
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10954-9. doi: 10.1073/pnas.95.18.10954.
The inducible isoform of the enzyme cyclooxygenase-2 (COX2) is an immediate early gene induced by synaptic activity in the brain. COX2 activity is an important mediator of inflammation, but it is not known whether COX2 activity is pathogenic in brain. To study the role of COX2 activity in ischemic injury in brain, expression of COX2 mRNA and protein and the effect of treatment with a COX2 inhibitor on neuronal survival in a rat model of global ischemia were determined. Expression of both COX2 mRNA and protein was increased after ischemia in CA1 hippocampal neurons before their death. There was increased survival of CA1 neurons in rats treated with the COX2-selective inhibitor SC58125 [1-[(4-methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl] pyrazole] before or after global ischemia compared with vehicle controls. Furthermore, hippocampal prostaglandin E2 concentrations 24 h after global ischemia were decreased in drug-treated animals compared with vehicle-treated controls. These results suggest that COX2 activity contributes to CA1 neuronal death after global ischemia.
环氧合酶-2（COX2）的诱导型同工酶是一种由大脑突触活动诱导的即早基因。COX2活性是炎症的重要介质，但尚不清楚COX2活性在大脑中是否具有致病性。为了研究COX2活性在脑缺血损伤中的作用，我们测定了COX2 mRNA和蛋白的表达以及COX2抑制剂处理对全脑缺血大鼠模型中神经元存活的影响。在CA1海马神经元死亡前，缺血后COX2 mRNA和蛋白的表达均增加。与溶剂对照组相比，在全脑缺血前后用COX2选择性抑制剂SC58125 [1-[(4-甲基磺酰基)苯基]-3-三氟甲基-5-[(4-氟)苯基]吡唑]处理的大鼠中，CA1神经元的存活率增加。此外，与溶剂处理的对照组相比，药物处理的动物在全脑缺血24小时后海马前列腺素E2浓度降低。这些结果表明，COX2活性促成了全脑缺血后CA1神经元的死亡。
