In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)

Autores
Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Lupu, Florea; Silasi Mansat, Robert; West, Melinda; Ramirez, Dario; Gomez-Mejiba, Sandra Esther; Bonini, Marcelo G.; Mason, Ronald P.; Garteiser P; Ehrenshaft, Marilyn; Hensley, Kenneth
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Free radicals associated with oxidative stress play a major role in amyotrophic lateral sclerosis (ALS). By combining immuno-spin trapping and molecular magnetic resonance imaging, in vivo trapped radical adducts were detected in the spinal cords of SOD1G93A-transgenic (Tg) mice, a model for ALS. For this study, the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) was administered (ip) over 5 days before administration (iv) of an anti-DMPO probe (anti-DMPO antibody covalently bound to an albumin–gadolinium–diethylenetriamine pentaacetic acid–biotin MRI contrast agent) to trap free radicals. MRI was used to detect the presence of the anti-DMPO radical adducts by a significant sustained increase in MR signal intensities (p < 0.05) or anti-DMPO probe concentrations measured from T1 relaxations (p < 0.01). The biotin moiety of the anti-DMPO probe was targeted with fluorescence-labeled streptavidin to locate the probe in excised tissues. Negative controls included either Tg ALS mice initially administered saline rather than DMPO followed by the anti-DMPO probe or non-Tg mice initially administered DMPO and then the anti-DMPO probe. The anti-DMPO probe was found to bind to neurons via colocalization fluorescence microscopy. DMPO adducts were also confirmed in diseased/nondiseased tissues from animals administered DMPO. Apparent diffusion coefficients from diffusion-weighted images of spinal cords from Tg mice were significantly elevated (p < 0.001) compared to wild-type controls. This is the first report regarding the detection of in vivo trapped radical adducts in an ALS model. This novel, noninvasive, in vivo diagnostic method can be applied to investigate the involvement of free radical mechanisms in ALS rodent models.
Fil: Towner, Rheal A.. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Smith, Nataliya. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Saunders, Debra. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Lupu, Florea. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Silasi Mansat, Robert. Oklahoma Medical Research Foundation; Estados Unidos
Fil: West, Melinda. National Institutes Of Health. Departament Of Healt & Human; Estados Unidos
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Bonini, Marcelo G.. University of Illinois; Estados Unidos
Fil: Mason, Ronald P.. National Institutes of Health; Estados Unidos
Fil: Garteiser P. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Ehrenshaft, Marilyn. National Institutes of Health; Estados Unidos
Fil: Hensley, Kenneth. University of Toledo; Estados Unidos
Materia
In vivo
Molecular magnetic resonance imaging
Immuno-spin trapping
Amyotrophic lateral sclerosis
Free radicals
DMPO
Anti-DMPO probe
Gd-DTPA–albumin–anti-DMPO–biotin probe
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/29295
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/29295
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)Towner, Rheal A.Smith, NataliyaSaunders, DebraLupu, FloreaSilasi Mansat, RobertWest, MelindaRamirez, DarioGomez-Mejiba, Sandra EstherBonini, Marcelo G.Mason, Ronald P.Garteiser PEhrenshaft, MarilynHensley, KennethIn vivoMolecular magnetic resonance imagingImmuno-spin trappingAmyotrophic lateral sclerosisFree radicalsDMPOAnti-DMPO probeGd-DTPA–albumin–anti-DMPO–biotin probehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Free radicals associated with oxidative stress play a major role in amyotrophic lateral sclerosis (ALS). By combining immuno-spin trapping and molecular magnetic resonance imaging, in vivo trapped radical adducts were detected in the spinal cords of SOD1G93A-transgenic (Tg) mice, a model for ALS. For this study, the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) was administered (ip) over 5 days before administration (iv) of an anti-DMPO probe (anti-DMPO antibody covalently bound to an albumin–gadolinium–diethylenetriamine pentaacetic acid–biotin MRI contrast agent) to trap free radicals. MRI was used to detect the presence of the anti-DMPO radical adducts by a significant sustained increase in MR signal intensities (p < 0.05) or anti-DMPO probe concentrations measured from T1 relaxations (p < 0.01). The biotin moiety of the anti-DMPO probe was targeted with fluorescence-labeled streptavidin to locate the probe in excised tissues. Negative controls included either Tg ALS mice initially administered saline rather than DMPO followed by the anti-DMPO probe or non-Tg mice initially administered DMPO and then the anti-DMPO probe. The anti-DMPO probe was found to bind to neurons via colocalization fluorescence microscopy. DMPO adducts were also confirmed in diseased/nondiseased tissues from animals administered DMPO. Apparent diffusion coefficients from diffusion-weighted images of spinal cords from Tg mice were significantly elevated (p < 0.001) compared to wild-type controls. This is the first report regarding the detection of in vivo trapped radical adducts in an ALS model. This novel, noninvasive, in vivo diagnostic method can be applied to investigate the involvement of free radical mechanisms in ALS rodent models.Fil: Towner, Rheal A.. Oklahoma Medical Research Foundation; Estados UnidosFil: Smith, Nataliya. Oklahoma Medical Research Foundation; Estados UnidosFil: Saunders, Debra. Oklahoma Medical Research Foundation; Estados UnidosFil: Lupu, Florea. Oklahoma Medical Research Foundation; Estados UnidosFil: Silasi Mansat, Robert. Oklahoma Medical Research Foundation; Estados UnidosFil: West, Melinda. National Institutes Of Health. Departament Of Healt & Human; Estados UnidosFil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Bonini, Marcelo G.. University of Illinois; Estados UnidosFil: Mason, Ronald P.. National Institutes of Health; Estados UnidosFil: Garteiser P. Oklahoma Medical Research Foundation; Estados UnidosFil: Ehrenshaft, Marilyn. National Institutes of Health; Estados UnidosFil: Hensley, Kenneth. University of Toledo; Estados UnidosElsevier2013-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/29295Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Lupu, Florea; Silasi Mansat, Robert; et al.; In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS); Elsevier; Free Radical Biology and Medicine; 63; 10-2013; 351-3600891-5849CONICET DigitalCONICETenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:24:46Zoai:ri.conicet.gov.ar:11336/29295instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:24:46.453CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
title In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
spellingShingle In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
Towner, Rheal A.
In vivo
Molecular magnetic resonance imaging
Immuno-spin trapping
Amyotrophic lateral sclerosis
Free radicals
DMPO
Anti-DMPO probe
Gd-DTPA–albumin–anti-DMPO–biotin probe
title_short In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
title_full In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
title_fullStr In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
title_full_unstemmed In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
title_sort In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS)
dc.creator.none.fl_str_mv Towner, Rheal A.
Smith, Nataliya
Saunders, Debra
Lupu, Florea
Silasi Mansat, Robert
West, Melinda
Ramirez, Dario
Gomez-Mejiba, Sandra Esther
Bonini, Marcelo G.
Mason, Ronald P.
Garteiser P
Ehrenshaft, Marilyn
Hensley, Kenneth
author Towner, Rheal A.
author_facet Towner, Rheal A.
Smith, Nataliya
Saunders, Debra
Lupu, Florea
Silasi Mansat, Robert
West, Melinda
Ramirez, Dario
Gomez-Mejiba, Sandra Esther
Bonini, Marcelo G.
Mason, Ronald P.
Garteiser P
Ehrenshaft, Marilyn
Hensley, Kenneth
author_role author
author2 Smith, Nataliya
Saunders, Debra
Lupu, Florea
Silasi Mansat, Robert
West, Melinda
Ramirez, Dario
Gomez-Mejiba, Sandra Esther
Bonini, Marcelo G.
Mason, Ronald P.
Garteiser P
Ehrenshaft, Marilyn
Hensley, Kenneth
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv In vivo
Molecular magnetic resonance imaging
Immuno-spin trapping
Amyotrophic lateral sclerosis
Free radicals
DMPO
Anti-DMPO probe
Gd-DTPA–albumin–anti-DMPO–biotin probe
topic In vivo
Molecular magnetic resonance imaging
Immuno-spin trapping
Amyotrophic lateral sclerosis
Free radicals
DMPO
Anti-DMPO probe
Gd-DTPA–albumin–anti-DMPO–biotin probe
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Free radicals associated with oxidative stress play a major role in amyotrophic lateral sclerosis (ALS). By combining immuno-spin trapping and molecular magnetic resonance imaging, in vivo trapped radical adducts were detected in the spinal cords of SOD1G93A-transgenic (Tg) mice, a model for ALS. For this study, the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) was administered (ip) over 5 days before administration (iv) of an anti-DMPO probe (anti-DMPO antibody covalently bound to an albumin–gadolinium–diethylenetriamine pentaacetic acid–biotin MRI contrast agent) to trap free radicals. MRI was used to detect the presence of the anti-DMPO radical adducts by a significant sustained increase in MR signal intensities (p < 0.05) or anti-DMPO probe concentrations measured from T1 relaxations (p < 0.01). The biotin moiety of the anti-DMPO probe was targeted with fluorescence-labeled streptavidin to locate the probe in excised tissues. Negative controls included either Tg ALS mice initially administered saline rather than DMPO followed by the anti-DMPO probe or non-Tg mice initially administered DMPO and then the anti-DMPO probe. The anti-DMPO probe was found to bind to neurons via colocalization fluorescence microscopy. DMPO adducts were also confirmed in diseased/nondiseased tissues from animals administered DMPO. Apparent diffusion coefficients from diffusion-weighted images of spinal cords from Tg mice were significantly elevated (p < 0.001) compared to wild-type controls. This is the first report regarding the detection of in vivo trapped radical adducts in an ALS model. This novel, noninvasive, in vivo diagnostic method can be applied to investigate the involvement of free radical mechanisms in ALS rodent models.
Fil: Towner, Rheal A.. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Smith, Nataliya. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Saunders, Debra. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Lupu, Florea. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Silasi Mansat, Robert. Oklahoma Medical Research Foundation; Estados Unidos
Fil: West, Melinda. National Institutes Of Health. Departament Of Healt & Human; Estados Unidos
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Bonini, Marcelo G.. University of Illinois; Estados Unidos
Fil: Mason, Ronald P.. National Institutes of Health; Estados Unidos
Fil: Garteiser P. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Ehrenshaft, Marilyn. National Institutes of Health; Estados Unidos
Fil: Hensley, Kenneth. University of Toledo; Estados Unidos
description Free radicals associated with oxidative stress play a major role in amyotrophic lateral sclerosis (ALS). By combining immuno-spin trapping and molecular magnetic resonance imaging, in vivo trapped radical adducts were detected in the spinal cords of SOD1G93A-transgenic (Tg) mice, a model for ALS. For this study, the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) was administered (ip) over 5 days before administration (iv) of an anti-DMPO probe (anti-DMPO antibody covalently bound to an albumin–gadolinium–diethylenetriamine pentaacetic acid–biotin MRI contrast agent) to trap free radicals. MRI was used to detect the presence of the anti-DMPO radical adducts by a significant sustained increase in MR signal intensities (p < 0.05) or anti-DMPO probe concentrations measured from T1 relaxations (p < 0.01). The biotin moiety of the anti-DMPO probe was targeted with fluorescence-labeled streptavidin to locate the probe in excised tissues. Negative controls included either Tg ALS mice initially administered saline rather than DMPO followed by the anti-DMPO probe or non-Tg mice initially administered DMPO and then the anti-DMPO probe. The anti-DMPO probe was found to bind to neurons via colocalization fluorescence microscopy. DMPO adducts were also confirmed in diseased/nondiseased tissues from animals administered DMPO. Apparent diffusion coefficients from diffusion-weighted images of spinal cords from Tg mice were significantly elevated (p < 0.001) compared to wild-type controls. This is the first report regarding the detection of in vivo trapped radical adducts in an ALS model. This novel, noninvasive, in vivo diagnostic method can be applied to investigate the involvement of free radical mechanisms in ALS rodent models.
publishDate 2013
dc.date.none.fl_str_mv 2013-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/29295
Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Lupu, Florea; Silasi Mansat, Robert; et al.; In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS); Elsevier; Free Radical Biology and Medicine; 63; 10-2013; 351-360
0891-5849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/29295
identifier_str_mv Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Lupu, Florea; Silasi Mansat, Robert; et al.; In Vivo Detection of Free Radicals using Molecular MRI and Immuno-Spin-Trapping in a Mouse Models for Amyotrophic Lateral Sclerosis (ALS); Elsevier; Free Radical Biology and Medicine; 63; 10-2013; 351-360
0891-5849
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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