Noninvasive assessment of the brain redox status after transient middle cerebral artery occlusion using Overhauser-enhanced magnetic resonance imaging
Noninvasive assessment of the brain redox status after transient middle cerebral artery occlusion using Overhauser-enhanced magnetic resonance imaging
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DOI：
10.1038/jcbfm.2009.84
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发表时间：
2009-10-01
影响因子：
6.3
通讯作者：
Utsumi, Hideo
中科院分区：
文献类型：
--
作者：
Yamato, Mayumi;Shiba, Takeshi;Utsumi, Hideo
氧化应激与脑缺血-再灌注后发生的细胞死亡有关，这导致活性氧的产生和抗氧化剂的减少，导致线粒体功能障碍。然而，用于收集这些证据的侵入性方法本身就是压力诱导，这可能会扭曲结果。在这项研究中，我们的目的是证明脑缺血再灌注后的氧化还原改变非侵入性，使用Overhauser增强磁共振成像。使用氧化还原敏感造影剂3-甲氧羰基-2，2，5，5-四甲基吡咯烷-L-氧基（甲氧羰基-PROXYL）的还原速率作为体内氧化还原状态的指标。短暂性大脑中动脉闭塞后，再灌注3小时后，未观察到抗氧化剂浓度、线粒体复合物活性或氧化还原状态图像强度的变化;然而，再灌注24小时后，根据连续图像计算的甲氧羰基-PROXYL还原率显著降低。与此一致的是，生化分析表明，抗坏血酸在缺血半球的浓度和线粒体复合物II的活性也有所下降。因此，脑氧化还原改变的非侵入性成像忠实地反映了缺血再灌注后抗氧化剂水平和线粒体复合物II活性的变化。脑血流与代谢杂志（2009）29，1655-1664; doi：10.1038/jcbfm.2009.84; 2009年6月24日在线发表
Oxidative stress has been implicated in the cell death that occurs after ischemia-reperfusion of the brain, which causes the production of reactive oxygen species and a decrease in antioxidants, leading to mitochondrial dysfunction. However, the invasive methods used to collect much of this evidence are themselves stress inducing, which could skew the results. In this study, we aimed at demonstrating brain redox alterations after ischemia-reperfusion noninvasively, using Overhauser-enhanced magnetic resonance imaging. The reduction rate of 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-L-oxyl (methoxycarbonyl-PROXYL), a redox-sensitive contrast agent, was used as an index of the redox status in vivo. No changes were observed in the antioxidant concentration, the mitochondrial complex activity, or in the redox status image intensity after 3 h of reperfusion, following transient middle cerebral artery occlusion; however, after 24 h of reperfusion, the methoxycarbonyl-PROXYL reduction rate, calculated from continuous images, had decreased significantly. Concordantly, biochemical assays showed that the concentration of ascorbic acid in the ischemic hemisphere and the activity of mitochondrial complex II had also decreased. Thus, the noninvasive imaging of the brain redox alterations faithfully reflected changes in antioxidant levels and in mitochondrial complex II activity after ischemia-reperfusion. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1655-1664; doi:10.1038/jcbfm.2009.84; published online 24 June 2009