Noninvasive assessment of the brain redox status in chronic kidney disease mouse using overhauser-enhanced magnetic resonance imaging

尿素毒素可能通过N-甲基-D-天冬氨酸（NMDA）受体的活性介导引起神经元的神经元损伤。本研究采用OMRI技术，以3-甲氧羰基-2，2，5，5-四甲基吡咯烷-1-氧基（3-methoxycarbonyl-2，2，5，5-tetramethylpyrrolidine-1-oxyl，methoxycarbonyl-PROXYL）为氧化还原敏感性对比剂，观察慢性肾脏病小鼠脑组织氧化还原状态的变化。在CKD发作后2周或4周，8-OHdG（8-羟基脱氧鸟苷）或记忆障碍未观察到变化，但在CKD 4周后，根据连续图像计算的甲氧羰基-PROXYL还原率显著增加。在CKD发病后8周，我们观察到8-OHdG免疫阳性细胞的数量增加和记忆障碍。因此，脑氧化还原改变的非侵入性成像与CKD引起脑损伤的初始阶段相关。

Urea toxin is suggested to be induced the glutamatergic neuronal damage mediated by the activity of N-methyl-D-aspartate (NMDA) receptor. In this study, we aimed to demonstrate brain redox alterations in chronic kidney disease mouse noninvasively, using overhauser-enhanced magnetic resonance imaging (OMRI).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 seen in the 8-OHdG (8-Hydroxydeoxyguanosine) or the memory disturbance at 2 or 4 weeks after CKD onset, but after 4 weeks of CKD, the methoxycarbonyl-PROXYL reduction rate, calculated from continuous images, had increased significantly. At 8 weeks after CKD onset, we observed an increase in the number of 8-OHdG-immunopositive cells and the disturbance in the memory. Thus, the noninvasive imaging of the brain redox alterations was associated with the initial stages of CKD cause brain injury.