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Updated: May 8, 2026
Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring
Published on: December 9, 2010
In vivo detection of free radicals in mouse septic encephalopathy using molecular MRI and immuno-spin trapping
Rheal A Towner1, Philippe Garteiser1, Fernando Bozza2
1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Abstract:
Free radicals are known to play a major role in sepsis. Combined immuno-spin trapping and molecular magnetic resonance imaging (MRI) was used to detect in vivo and in situ levels of free radicals in murine septic encephalopathy after cecal ligation and puncture (CLP). DMPO (5,5-dimethyl pyrroline N-oxide) was injected over 6h after CLP, before administration of an anti-DMPO probe (anti-DMPO antibody bound to albumin-gadolinium-diethylene triamine pentaacetic acid-biotin MRI targeting contrast agent). In vitro assessment of the anti-DMPO probe in oxidatively stressed mouse astrocytes significantly decreased T1 relaxation (p < 0.0001) compared to controls. MRI detected the presence of anti-DMPO adducts via a substantial decrease in %T1 change within the hippocampus, striatum, occipital, and medial cortex brain regions (p < 0.01 for all) in septic animals compared to shams, which was sustained for over 60 min (p < 0.05 for all). Fluorescently labeled streptavidin was used to target the anti-DMPO probe biotin, which was elevated in septic brain, liver, and lungs compared to sham. Ex vivo DMPO adducts (qualitative) and oxidative products, including 4-hydroxynonenal and 3-nitrotyrosine (quantitative, p < 0.05 for both), were elevated in septic brains compared to shams. This is the first study that has reported on the detection of in vivo and in situ levels of free radicals in murine septic encephalopathy.
Insights
This study detected free radicals in septic encephalopathy using immuno-spin trapping and MRI. Elevated oxidative stress markers were found in the brains of septic mice, confirming free radical involvement.
Area of Science:
- Biomedical Imaging
- Neuroscience
- Free Radical Biology
Background:
- Sepsis-induced encephalopathy involves significant oxidative stress.
- Free radicals are implicated in the pathogenesis of sepsis.
Purpose of the Study:
- To detect in vivo and in situ levels of free radicals in murine septic encephalopathy.
- To investigate the role of free radicals in brain dysfunction during sepsis.
Main Methods:
- Combined immuno-spin trapping with molecular MRI using a novel anti-DMPO probe.
- Administered DMPO (5,5-dimethyl pyrroline N-oxide) and an albumin-gadolinium-biotin MRI contrast agent.
- Assessed probe efficacy in vitro and MRI signal changes in vivo in septic mice.
Main Results:
- The anti-DMPO probe significantly decreased T1 relaxation in vitro.
- MRI detected elevated anti-DMPO adducts in multiple brain regions of septic mice.
- Elevated oxidative stress markers (4-hydroxynonenal, 3-nitrotyrosine) were found in septic brains.
Conclusions:
- This study demonstrates the first detection of in vivo and in situ free radicals in murine septic encephalopathy.
- The findings highlight the critical role of free radicals in sepsis-induced brain injury.
- Combined immuno-spin trapping and MRI is a viable method for studying oxidative stress in sepsis.
