Decreased peripheral nerve damage after ischemia-reperfusion injury in mice lacking TNF-alpha

Decreased peripheral nerve damage after ischemia-reperfusion injury in mice lacking TNF-alpha
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DOI:
10.1016/j.jns.2007.10.004
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发表时间:
2008-04-15
影响因子:
4.4
通讯作者:
Low, Phillip A.
Low, Phillip A.
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Yanping;Kawamura, Nobutoshi;Low, Phillip A.

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我们试图探讨肿瘤坏死因子- α (tnf - α)在周围神经缺血再灌注(IR)损伤的发病机制中的作用。我们建立了野生型(WT)和tnf - α敲除(KO)小鼠的缺血再灌注模型。通过电生理、行为评分和形态学指标(水肿和缺血性纤维变性[IFD])检测tnf - α对缺血再灌注后周围神经结构和功能的影响。免疫组化检测tnf - α和核因子κ B (nf - κ B)的表达。与WT相比,TNF-alpha KO小鼠的坐骨神经病理有明显改善。这是一个遭受中度缺血再灌注损伤的区域。电生理及部分行为学指标均有明显改善。IR后WT小鼠坐骨-胫骨神经中tnf - α和nf - κ B表达丰富,而KO小鼠缺血神经中tnf - α表达较少或完全缺失。我们得出结论,tnf - α在周围神经缺血-再灌注损伤的发病机制中起重要作用,可能部分通过NF-kappa b的激活。
We sought to explore the role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of peripheral nerve ischemia-reperfusion (IR) injury. We established an ischemia-reperfusion model in wild type (WT) and TNF-alpha knockout (KO) mice. Electrophysiology, behavioral score and morphological indices (edema and ischemic fiber degeneration [IFD]) were examined to determine the influence of TNF-alpha on peripheral nerve structure and function following ischemia followed by reperfusion. TNF-alpha and nuclear factor-kappa B (NF-kappa B) expression wereevaluated using immunohistochemistry. TNF-alpha KO mice, compared to WT had, in sciatic nerve, marked improvement in nerve pathology. This is a region subject to moderate ischemia-reperfusion injury. There was also a significant improvement in electrophysiological and some behavioral indices. TNF-alpha and NF-kappa B expression were abundant in sciatic-tibial nerves of WT mice subjected to IR, but there was less, or complete lack of, expression in ischemic nerve of TNF-alpha KO mice. We conclude that TNF-alpha plays an essential role in the pathogenesis of peripheral nerve ischemia-reperfusion injury, possibly partly through the activation of NF-kappa B. (C) 2007 Elsevier B.V. All rights reserved.