期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 74, 期 -, 页码 222-228出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.06.026
关键词
Blood-brain barrier; Oxidative stress; In vivo EPR imaging; Nitroxide; Redox status; Free radicals
资金
- Japanese Society for the Promotion of Science [24791318, 22390236]
- Grants-in-Aid for Scientific Research [24791318, 22390236] Funding Source: KAKEN
Electron paramagnetic resonance (EPR) imaging using nitroxides as redox-sensitive probes is a powerful, noninvasive method that can be used under various physiological conditions to visualize changes in redox status that result from oxidative damage. Two blood-brain barrier-permeative nitroxides, 3-hydroxymethy1-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbony1-2,2,5,5-tetramethy (MCP), have been widely used as redox-sensitive probes in the brains of small animals, but their in vivo distribution and properties have not yet been analyzed in detail. In this study, a custom-made continuous-wave three-dimensional (3D) EPR imager was used to obtain 3D EPR images of mouse heads using MCP or HMP. This EPR imager made it possible to take 3D EPR images reconstructed from data from 181 projections acquired every 60 s. Using this improved EPR imager and magnetic resonance imaging, the distribution and reduction time courses of HMP and MCP were examined in mouse heads. EPR images of living mice revealed that HMP and MCP have different distributions and different time courses for entering the brain. Based on the pharmacokinetics of the reduction reactions of HMP and MCP in the mouse head, the half-lives of HMP and MCP were clearly and accurately mapped pixel by pixel. An ischemic mouse model was prepared, and the half-life of MCP was mapped in the mouse head. Compared to the half-life in control mice, the half-life of MCP in the ischemic model mouse brain was significantly increased, suggesting a shift in the redox balance. This in vivo EPR imaging method using BBB-permeative MCP is a useful noninvasive method for assessing changes in the redox status in mouse brains under oxidative stress. (C) 2014 Elsevier Inc. All rights reserved.
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