Hickey Robert W, Adelson P David, Johnnides Michael J, Davis Dwight S, Yu Zhisheng, Rose Marie E, Chang Yue-Fang, Graham Steven H
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Pediatr Res. 2007 Sep;62(3):271-6. doi: 10.1203/PDR.0b013e3180db2902.
Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins. COX-2, the predominant COX isoform in brain, is induced by synaptic activity. COX-2-generated prostaglandins are important regulators for a range of activities under physiologic conditions. However, under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that can exacerbate brain injury. In this study, we examine the developmental production of COX-2 and test the ability of a COX-2 inhibitor, SC58125, to attenuate traumatic brain injury in developing rats. We show that constitutive COX-2 concentration is low (0.5-fold adult concentration) during the first postnatal week and then increases to 3-fold of adult levels between days 14-60. Controlled cortical impact (CCI) at postnatal day (PND) 17, but not PND 7, caused an additional 3-fold increase in COX-2 content and was associated with an increase in the COX-2 product PGE2. Treatment with the COX-2 inhibitor SC58125 in PND17 rats exposed to CCI attenuated the rise in PGE2 but did not attenuate lesion volume or improve performance in the Morris water maze.
环氧化酶（COX）是前列腺素生成过程中的限速酶。COX-2是大脑中主要的COX同工型，由突触活动诱导产生。COX-2生成的前列腺素是生理条件下一系列活动的重要调节因子。然而，在病理条件下，COX-2活性可产生活性氧和有毒的前列腺素代谢产物，从而加重脑损伤。在本研究中，我们检测了COX-2在发育过程中的产生情况，并测试了COX-2抑制剂SC58125减轻发育中大鼠创伤性脑损伤的能力。我们发现，出生后第一周内，COX-2的组成型浓度较低（为成年浓度的0.5倍），然后在第14 - 60天之间增加到成年水平的3倍。出生后第17天（PND17）而非第7天进行控制性皮质撞击（CCI），导致COX-2含量额外增加3倍，并与COX-2产物前列腺素E2（PGE2）的增加有关。在暴露于CCI的PND17大鼠中用COX-2抑制剂SC58125治疗可减弱PGE2的升高，但不能减小损伤体积或改善莫里斯水迷宫中的表现。
