Temporal and Spatial Dynamics of Peroxynitrite-Induced Oxidative Damage after Spinal Cord Contusion Injury
Temporal and Spatial Dynamics of Peroxynitrite-Induced Oxidative Damage after Spinal Cord Contusion Injury
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DOI：
10.1089/neu.2008.0870
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发表时间：
2009-08-01
影响因子：
4.2
通讯作者：
Hall, Edward D.
中科院分区：
文献类型：
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作者：
Carrico, Kimberly M.;Vaishnav, Radhika;Hall, Edward D.
过氧亚硝酸盐(PN)被认为是急性脊髓损伤(SCI)后继发性氧化损伤的重要介质。PN分解产物二氧化氮(中心点NO2)、羟基自由基(中心点OH)和碳酸盐自由基(中心点CO3)与细胞脂质和蛋白质高度反应。在这项免疫组织化学研究中，我们使用3-硝基酪氨酸(3-NT)和4-羟基壬烯醛(4-HNE)对挫伤大鼠胸段脊髓(IH装置，200kdyn，T10)中PN介导的氧化损伤进行了时间和空间关系的研究。3-NT或4-HNE免疫组织化学染色仅见于未损伤的假脊髓。相反，这两个标记物在震中后3小时显示显著增加，延伸到整个灰质和周围的白质。在24和72h，氧化损伤沿周向扩展，除损伤部位有一小片白质组织外，其余白质组织均受累，沿吻侧和尾侧方向纵向可达6~9 mm。在神经元胞体、轴突和微血管中观察到染色。除3h外，各时间点3-NT和4-HNE染色的平均吻侧或尾侧范围无显著差异。1周后，氧化损伤染色的纵向范围大大减少，2周时更是如此。3-NT和4-HNE染色的空间和时间重叠支持了PN参与脂质过氧化和蛋白质硝化所产生的损伤的概念，以及针对PN或PN衍生的自由基的抗氧化剂如果在损伤后的第一个小时内使用，应该是有效的神经保护剂。
The reactive nitrogen species peroxynitrite (PN) has been suggested to be an important mediator of the secondary oxidative damage that occurs following acute spinal cord injury (SCI). The PN decomposition products nitrogen dioxide (center dot NO2), hydroxyl radical (center dot OH), and carbonate radical (center dot CO3) are highly reactive with cellular lipids and proteins. In this immunohistochemical study, we examined the temporal (3, 24, and 72 h, and 1 and 2 weeks) and spatial relationships of PN-mediated oxidative damage in the contusion-injured rat thoracic spinal cord (IH device, 200 kdyn, T10) using 3-nitrotyrosine (3-NT), a marker for protein nitration by PN-derived center dot NO2 and 4-hydroxynonenal (4-HNE), an indicator of lipid peroxidation (LP) initiated by any of the PN radicals. Minimal 3-NT or 4-HNE immunostaining was seen in sham, non-injured spinal cords. In contrast, both markers showed a substantial increase at 3 h post-injury at the epicenter, that extended throughout the gray matter and into the surrounding white matter. At 24 and 72 h, the oxidative damage expanded circumferentially to involve all but a small rim of white matter tissue at the injury site, and longitudinally as much as 6-9 mm in the rostral and caudal directions. The staining was observed in neuronal soma, axons, and microvessels. At all time points except 3 h, there was no significant difference in the mean rostral or caudal extent of 3-NT and 4-HNE staining. By 1, and more so at 2 weeks, the longitudinal extent of the oxidative damage staining was greatly decreased. The spatial and temporal overlap of 3-NT and 4-HNE staining supports the concept that PN is involved in both damage produced by lipid peroxidation and protein nitration, and that antioxidant agents that target PN or PN-derived radicals should be effective neuroprotectants for acute SCI if administered during the first post-injury hours.