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Abstract #1873

in vivo Detection of Membrane-Bound Radicals in Mouse Brains with Sepsis Using Molecular MRI and Immuno-Spin-Trapping

Rheal A. Towner1, Nataliya Smith1, Philippe Garteiser1, Debra Saunders1, Florea Lupu2, Robert Silasi-Mansat2, Dario C. Ramirez3, Sandra E. Gomez-Mejiba3, Ronald P. Mason4, Marilyn I. Ehrenshaft4, Fernando Bozza5, Marcus Frenandes de Oliveira6, Hugo C. Castro Faria-Neto7

1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States; 2Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States; 3Laboratory of Experimental and Therapeutic Medicine, National University of San Luis, San Luis, Argentina; 4Laboratory of Pharmacology & Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States; 5Instituto de Pesquisa Clinica Evandro Chagas, Fundao Oswaldo Cruz, Rio de Janeiro, RJ, Brazil; 6Instituto de Bioqumica Mdica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 7Instituto de Pesquisa Clinica Evandro Chagas, Fundao Oswaldo Cruz, Rio de Janeiro, Brazil

Oxidative stress from free radicals plays a major role in sepsis. A combination of immuno-spin-trapping (IST) and targeted molecular magnetic resonance imaging (mMRI) was used to detect in vivo levels of membrane-bound radicals (MBR) in brain tissues from mice with cecal ligation puncture (CLP)-induced sepsis. The spin trapping compound DMPO (5,5-dimethyl pyrroline N-oxide) was used to trap radicals. An anti-DMPO probe (anti-DMPO antibody covalently bound to an albumin-Gd-DTPA-biotin construct was used to detect MBR in vivo with mMRI. This method can be applied towards any radical-associated pathological condition for the in vivo assessment of membrane-bound protein and/or lipid radical levels.

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Keywords

acquisition acute addition adducts administered advanced agent albumin animal animals anti antibodies antibody anticipated applied binds biotin bound bovine brain brains cardiovascular cecum city closed combination computed conditions content contrast control controls cortex decrease detect detected detecting detection differentiation disease environment environmental equation events every evolution except experimental exposed extent federal fitting form foundation free funding funds growth health hours in vivo indicated induced injected injection intensity intervals invasive involved junction laboratory ligated ligation lipid lobe magnet major male maps mason measured mechanisms medial medical medicine membrane mica mice microscopy model molecular mouse muscle national neurological nonlinear novel occipital omitted organs outlined oxidative oxidatively park period pixel plays prepared previously probe procedures processed protein protocol puncture radical radicals rapid regarding regional repetition report response returned role samples sepsis septic serum sham significantly silk spatial spin squeezed sterile subjected substantial synthesis system taken target targeting technologies timing tissues towner transverse triangle understanding units vitro