Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent
Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent
复制标题
DOI：
10.1038/jcbfm.2008.5
复制
发表时间：
2008-06-01
影响因子：
6.3
通讯作者：
Krishna, Murali C.
中科院分区：
文献类型：
--
作者：
Hyodo, Fuminori;Chuang, Kai-Hsiang;Krishna, Murali C.
活性氧（ROS）和受损的抗氧化防御可能会导致脑疾病，如中风，肌萎缩侧索硬化症等。氮氧化物是氧化还原敏感的顺磁性造影剂和抗氧化剂。测试了血脑屏障（BBB）可渗透的氮氧化物甲氧基羰基-2，2，5，5-四甲基吡咯烷-1-氧基（MC-P）作为磁共振成像（MRI）造影剂用于脑组织氧化还原成像的能力。通过MRI使用快速Look-PART（1）-映射序列定量啮齿动物脑中的MC-P松弛。在大脑皮层和丘脑中，注射MC-P后MRI信号强度增加了50%，但当使用BBB不可渗透的氮氧化物3CxP（3-羧基-2，2，5，5，5-四甲基吡咯烷-1-氧基）时仅增加了2.7%。MC-P注射后丘脑和大脑皮质中的最大浓度计算值分别为1.9 +/- 0.35和3.0 +/- 0.50 mmol/ L。这些值与通过电子顺磁共振（EPR）光谱获得的脑组织和血液浓度的离体数据一致。此外，MC-P的减少率显着降低后再灌注短暂MCAO（大脑中动脉闭塞），氧化损伤导致的氧化还原状态的变化相关的条件。这些结果显示了BBB可渗透的氮氧化物作为MRI造影剂和抗氧化剂的用途，以评估ROS在神经系统疾病中的作用。
Reactive oxygen species (ROS) and compromised antioxidant defense may contribute to brain disorders such as stroke, amyotrophic lateral sclerosis, etc. Nitroxides are redox-sensitive paramagnetic contrast agents and antioxidants. The ability of a blood - brain barrier (BBB)permeable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-P), as a magnetic resonance-imaging (MRI) contrast agent for brain tissue redox imaging was tested. MC-P relaxation in rodent brain was quantified by MRI using a fast Look-Locker T(1)-mapping sequence. In the cerebral cortex and thalamus, the MRI signal intensity increased up to 50% after MC-P injection, but increased only by 2.7% when a BBB-impermeable nitroxide, 3CxP (3-carboxy-2,2,5,5,5-tetramethylpyrrolidine-1- oxyl) was used. The maximum concentrations in the thalamus and cerebral cortex after MC-P injection were calculated to be 1.9 +/- 0.35 and 3.0 +/- 0.50 mmol/ L, respectively. These values were consistent with the ex vivo data of brain tissue and blood concentration obtained by electron paramagnetic resonance (EPR) spectroscopy. Also, reduction rates of MC-P were significantly decreased after reperfusion following transient MCAO (middle cerebral artery occlusion), a condition associated with changes in redox status resulting from oxidative damage. These results show the use of BBB-permeable nitroxides as MRI contrast agents and antioxidants to evaluate the role of ROS in neurologic diseases.