期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 32, 期 1, 页码 23-32出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2011.119
关键词
fluorescence lifetime; inflammatory; in vivo; molecular imaging; time domain
资金
- NIH [S10 RR22599-01A1, R21AG030320]
- ICMIC [NCI-P50-CA128346]
- IVISR
- Larry L Hillblom Foundation
- [T35AG026757]
Superoxide is the single-electron reduction product of molecular oxygen generated by mitochondria and the innate immune enzyme complex, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and its isoforms. Initially identified as critical to the host defense against infection, superoxide has recently emerged as an important signaling molecule and as a proposed mediator of central nervous system injury in stroke, neurodegenerative conditions, and aging itself. Complete understanding of superoxide in central nervous system disease has been hampered by lack of noninvasive imaging techniques to evaluate this highly reactive, short-lived molecule in vivo. Here we describe a novel optical imaging technique to monitor superoxide real time in intact animals using a fluorescent probe compound and fluorescence lifetime contrast-based unmixing. Specificity for superoxide was confirmed using validated mouse models with enhanced or attenuated brain superoxide production. Application of fluorescence lifetime unmixing removed autofluorescence, further enhanced sensitivity and specificity of the technique, permitted visualization of physiologically relevant levels of superoxide, and allowed superoxide in specific brain regions (e.g., hippocampus) to be mapped. Lifetime contrast-based unmixing permitted disease model-specific and brain region-specific differences in superoxide levels to be observed, suggesting this approach may provide valuable information on the role of mitochondrial and Nox-derived superoxide in both normal function and pathologic conditions in the central nervous system. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 23-32; doi:10.1038/jcbfm.2011.119; published online 17 August 2011
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