Kunz Tina, Marklund Niklas, Hillered Lars, Oliw Ernst H
Department of Pharmaceutical Biosciences, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
J Neurotrauma. 2002 Sep;19(9):1051-64. doi: 10.1089/089771502760341965.
Inflammatory mediators are important in traumatic brain injury (TBI). The objective of the present study was to investigate the expression of cyclooxygenase-2 (COX-2), prostaglandin E (PGE) and PGD synthases, and PGH2 metabolism in two rat models of TBI. Fluid percussion injury (FPI) resulted in bilateral induction of COX-2 mRNA in the dentate gyri and the cortex, whereas controlled cortical contusion injury (CCC) induced COX-2 mRNA in the ipsilateral dentate gyrus and intensely in the cortex as judged by in situ hybridization. The induction subsided within 24 h. COX-2 immunoreactivity was detectable in these areas and persisted in the ipsilateral cortex for at least 72 h after CCC. Regions with COX-2 induction co-localized with TUNEL staining, suggesting a link between COX-2 expression and cell damage. COX-2 forms PGH2, which can be isomerized to PGD2, PGE2, and PGF2alpha by enzymatic and non-enzymatic mechanisms. In situ hybridization showed that mRNA of PGD synthase and microsomal PGE synthase were present in the choroid plexus. The microsomal PGE synthase was induced bilaterally after FPI and unilaterally after CCC. Liquid chromatography-mass spectrometry showed that low speed supernatant of normal and traumatized cortex and hippocampus transformed PGH2 to PGD2 as main product. PGD2 was dehydrated in brain homogenates to biological active compounds, for example, 15-deoxy-delta12,14-PGJ2. Thus COX-2 increases in certain neurons following TBI without neuronal induction of PGD and microsomal PGE synthases, suggesting that PGH2 may decompose to PGD2 and its dehydration products by nonenzymatic mechanisms or to PGD2 by low constitutive levels of PGD synthase.
炎症介质在创伤性脑损伤（TBI）中起着重要作用。本研究的目的是调查环氧化酶-2（COX-2）、前列腺素E（PGE）和PGD合酶的表达以及PGH2代谢在两种TBI大鼠模型中的情况。液压冲击伤（FPI）导致齿状回和皮质中COX-2 mRNA的双侧诱导，而通过原位杂交判断，控制性皮质撞击伤（CCC）诱导同侧齿状回中COX-2 mRNA表达，并在皮质中强烈诱导。诱导在24小时内消退。在这些区域可检测到COX-2免疫反应性，并且在CCC后同侧皮质中持续至少72小时。COX-2诱导区域与TUNEL染色共定位，表明COX-2表达与细胞损伤之间存在联系。COX-2形成PGH2，其可通过酶促和非酶促机制异构化为PGD2、PGE2和PGF2α。原位杂交显示脉络丛中存在PGD合酶和微粒体PGE合酶的mRNA。微粒体PGE合酶在FPI后双侧诱导，在CCC后单侧诱导。液相色谱-质谱分析表明，正常和创伤皮质及海马的低速上清液将PGH2转化为主要产物PGD2。PGD2在脑匀浆中脱水形成生物活性化合物，例如15-脱氧-Δ12,14-PGJ2。因此，TBI后某些神经元中COX-2增加，而PGD和微粒体PGE合酶未被神经元诱导，这表明PGH2可能通过非酶促机制分解为PGD2及其脱水产物，或通过低水平组成型PGD合酶分解为PGD2。
