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

尿素毒素可通过N-甲基-D-天冬氨酸(NMDA)受体的活性诱导谷氨酸能神经元损伤。在这项研究中，我们旨在利用Overhauser增强磁共振成像(OMRI)无创性地显示慢性肾脏疾病小鼠脑内氧化还原的变化。以氧化还原敏感的造影剂3-methoxycarbonyl-2，2，5，5-tetramethylpyrrolidine-l-oxyl的减少率作为体内氧化还原状态的指标。CKD发病后2周和4周，8-羟基鸟苷(8-OHdG)和记忆障碍无明显变化，但CKD发病4周后，由连续图像计算的甲氧羰基-丙氧基还原速率显著增加。在CKD发病8周后，我们观察到8-OHdG免疫阳性细胞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引起脑损伤的早期阶段有关。

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.