Regional expression and role of cyclooxygenase-2 following experimental traumatic brain injury
Regional expression and role of cyclooxygenase-2 following experimental traumatic brain injury
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DOI：
10.1089/neu.2000.17.69
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发表时间：
2000-01-01
影响因子：
4.2
通讯作者：
Moore, AN
中科院分区：
文献类型：
--
作者：
Dash, PK;Mach, SA;Moore, AN
前列腺素是一种强有力的炎症介质，由花生四烯酸（AA）通过环氧化酶-1和-2（考克斯-1和考克斯-2）的作用产生。在这项研究中，我们报告了大鼠外侧皮质撞击伤后，损伤部位周围皮质和同侧海马中考克斯-2蛋白水平显著增加。考克斯-2蛋白表达在伤后3 h即开始升高，并持续3d。不仅在相邻的皮质和海马中检测到免疫反应性增加，而且在对侧皮质和海马、同侧梨状皮质和同侧杏仁复合体中也观察到免疫反应性增加。考克斯-2免疫反应细胞形态正常，不存在任何凋亡的特征。使用神经元特异性或星形胶质细胞特异性标记物的双重免疫染色实验表明，考克斯-2的表达几乎只局限于神经元细胞。给予考克斯-2抑制剂4-[5-（4-甲基苯基）-3-（三氟甲基）-H-1-吡唑-1-基]苯磺酰胺（塞来昔布，以Celebrex销售）可降低运动功能，但不影响认知功能，表明创伤性脑损伤后考克斯-2诱导可能起保护作用。
Prostaglandins, potent mediators of inflammation, are generated from arachidonic acid (AA) via the action of cyclooxygenase-1 and -2 (COX-1 and COX-2), In this study, we report that lateral cortical impact injury in rats significantly increases COX-2 protein levels both in the cortex surrounding the injury site and the ipsilateral hippocampus. COX-2 protein level was elevated as early as 3 h postinjury and persisted for up to 3 days. Increases in immunoreactivity were detected not only in the adjacent cortex and hippocampus, but were also observed in the contralateral cortex and hippocampus, the ipsilateral piriform cortex and the ipsilateral amygdaloid complex. COX-2 immunoreactive cells appear morphologically normal and do not present any of the characteristic features of apoptosis. Double immunostaining experiments using either a neuron-specific or an astroglial-specific marker show that the expression of COX-2 is localized almost exclusively in neuronal cells. Administration of the COX-2 inhibitor 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-H-1-pyrazol-1-yl]benzenesulfonamide (celecoxib, marketed as Celebrex) worsens motor, but not cognitive, performance, suggesting that COX-2 induction following traumatic brain injury may play a protective role.