Temporal modulation of cytokine expression following focal cerebral ischemia in mice
Temporal modulation of cytokine expression following focal cerebral ischemia in mice
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DOI：
10.1016/s0006-8993(98)01140-8
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发表时间：
1999-02-27
期刊：
影响因子：
2.9
通讯作者：
Eckenstein, FP
中科院分区：
文献类型：
--
作者：
Hill, JK;Gunion-Rinker, L;Eckenstein, FP
越来越多的证据表明，炎症反应在中枢神经系统缺血中起着重要作用。然而，小鼠模型的局灶性缺血，仍然不完全的特点。在这项研究中，我们研究了几种细胞因子和血管粘附分子E-选择素的表达，以表征C57 BL/6 J小鼠中风后的分子事件。使用多探针RNA酶保护测定（RPA），在小鼠大脑中动脉永久性和暂时性闭塞后分析19种细胞因子的mRNA。另外，通过逆转录-聚合酶链反应（RT-PCR）分析来自相同小鼠的样品以评估E-选择素mRNA表达水平。几种细胞因子mRNA在永久性和短暂性CNS缺血中表现出相似的表达模式，而其他细胞因子则表现出依赖于卒中类型的时间表达模式。对于这两种模型，TNF α的mRNA水平在早期（4小时）升高，随后是IL-6（10-18小时）和TGF β 1的相对晚期（96小时）升高。IL-1 α、IL-1 β和IL-1 ra水平显示时间表达的模型依赖性变化。再灌注似乎延迟了这些细胞因子的诱导。缺血性损伤后，小鼠CNS中细胞因子mRNA表达发生时间变化。我们的研究结果证明了多探针RPA用于评价细胞因子mRNA水平变化的实用性和能力。此外，这项研究是，据我们所知，第一次显示在小鼠脑缺血细胞因子mRNA的时间变化，形成了进一步探索这些细胞因子在调节缺血性神经元损伤在这个模型中的作用的基础。(C)1999 Elsevier Science B. V.保留所有权利。
There is increasing evidence that the inflammatory response plays an important role in CNS ischemia. The murine model of focal ischemia, however, remains incompletely characterized. In this study we examined expression of several cytokines and the vascular adhesion molecule E-selectin, in order to characterize the molecular events following stroke in the C57BL/6J mouse. Using a multi-probe RNAse protection assay (RPA), mRNA for 19 cytokines was analyzed following permanent and transient occlusion of the middle cerebral artery in mice. In addition, samples from the same mice were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate E-selectin mRNA expression levels. Several cytokine mRNAs showed a similar expression pattern in both permanent and transient CNS ischemia while others showed a temporal expression pattern that was dependent on the type of stroke. For both models, mRNA levels of TNF alpha rose early (4 h) followed by IL-6 (10-18 h) and a comparatively late increase (96 h) in TGF beta 1. IL-1 alpha, IL-1 beta and IL-1ra levels showed a model dependent shift in temporal expression. Reperfusion appeared to delay the induction of these cytokines. Temporal changes in cytokine mRNA expression in the mouse CNS occur following ischemic damage. Our findings demonstrate the utility and power of multi-probe RPA for evaluation of changes in cytokine mRNA levels. Moreover, this study is, to our knowledge the first to show temporal changes in cytokine mRNA in mouse cerebral ischemia, forming a basis for further exploration of the roles of these cytokines in modulating ischemic neuronal damage in this model. (C) 1999 Elsevier Science B.V. All rights reserved.