Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury

Reactive gliosis is a key feature and an important pathophysiological mechanism underlying chronic neurodegeneration following traumatic brain injury (TBI). In this study, we have explored the effects of intramuscular IGF-1 gene therapy on reactive gliosis and functional outcome after an injury of t...

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Autores: Herrera, Macarena, Bandín, S., Champarini, L.G., Hereñú, C.B., Bellini, María José
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/259677
Acesso em linha:http://hdl.handle.net/10261/259677
Access Level:Acceso aberto
Palavra-chave:Astrocytes
IGF-1
Microglia
Neuroinflammation
Neuroprotection
Traumatic brain injury.
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spelling Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injuryHerrera, MacarenaBandín, S.Champarini, L.G.Hereñú, C.B.Bellini, María JoséAstrocytesIGF-1MicrogliaNeuroinflammationNeuroprotectionTraumatic brain injury.Reactive gliosis is a key feature and an important pathophysiological mechanism underlying chronic neurodegeneration following traumatic brain injury (TBI). In this study, we have explored the effects of intramuscular IGF-1 gene therapy on reactive gliosis and functional outcome after an injury of the cerebral cortex. Young adult male rats were intramuscularly injected with a recombinant adenoviral construct harboring the cDNA of human IGF-1 (RAd-IGF1), with a control vector expressing green fluorescent protein (RAd-GFP) or PBS as control. Three weeks after the intramuscular injections of adenoviral vectors, animals were subjected to a unilateral penetrating brain injury. The data revealed that RAd-IGF1 gene therapy significantly increased serum IGF1 levels and improved working memory performance after one week of TBI as compared to PBS or RAd-GFP lesioned animals. At the same time, when we analyzed the effects of therapy on glial scar formation, the treatment with RAd-IGF1 did not modify the number of glial fibrillary acidic protein (GFAP) positive cells, but we observed a decrease in vimentin immunoreactive astrocytes at 7 days post-lesion in the injured hemisphere compared to RAd-GFP group. Moreover, IGF-1 gene therapy reduced the number of Iba1+ cells with reactive phenotype and the number of MHCII + cells in the injured hemisphere. These results suggest that intramuscular IGF-1 gene therapy may represent a new approach to prevent traumatic brain injury outcomes in rats.This research was funded by grant PIP 0618 from CONICET, Argentina to MJB and by grant PICT-2018-02446 Plan Argentina Innovadora from Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación to CBH.ElsevierConsejo Nacional de Investigaciones Científicas y Técnicas (Argentina)Agencia Nacional de Promoción Científica y Tecnológica (Argentina)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/259677reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.brainresbull.2021.07.023Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2596772026-05-22T06:33:51Z
dc.title.none.fl_str_mv Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
title Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
spellingShingle Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
Herrera, Macarena
Astrocytes
IGF-1
Microglia
Neuroinflammation
Neuroprotection
Traumatic brain injury.
title_short Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
title_full Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
title_fullStr Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
title_full_unstemmed Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
title_sort Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
dc.creator.none.fl_str_mv Herrera, Macarena
Bandín, S.
Champarini, L.G.
Hereñú, C.B.
Bellini, María José
author Herrera, Macarena
author_facet Herrera, Macarena
Bandín, S.
Champarini, L.G.
Hereñú, C.B.
Bellini, María José
author_role author
author2 Bandín, S.
Champarini, L.G.
Hereñú, C.B.
Bellini, María José
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina)
Agencia Nacional de Promoción Científica y Tecnológica (Argentina)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Astrocytes
IGF-1
Microglia
Neuroinflammation
Neuroprotection
Traumatic brain injury.
topic Astrocytes
IGF-1
Microglia
Neuroinflammation
Neuroprotection
Traumatic brain injury.
description Reactive gliosis is a key feature and an important pathophysiological mechanism underlying chronic neurodegeneration following traumatic brain injury (TBI). In this study, we have explored the effects of intramuscular IGF-1 gene therapy on reactive gliosis and functional outcome after an injury of the cerebral cortex. Young adult male rats were intramuscularly injected with a recombinant adenoviral construct harboring the cDNA of human IGF-1 (RAd-IGF1), with a control vector expressing green fluorescent protein (RAd-GFP) or PBS as control. Three weeks after the intramuscular injections of adenoviral vectors, animals were subjected to a unilateral penetrating brain injury. The data revealed that RAd-IGF1 gene therapy significantly increased serum IGF1 levels and improved working memory performance after one week of TBI as compared to PBS or RAd-GFP lesioned animals. At the same time, when we analyzed the effects of therapy on glial scar formation, the treatment with RAd-IGF1 did not modify the number of glial fibrillary acidic protein (GFAP) positive cells, but we observed a decrease in vimentin immunoreactive astrocytes at 7 days post-lesion in the injured hemisphere compared to RAd-GFP group. Moreover, IGF-1 gene therapy reduced the number of Iba1+ cells with reactive phenotype and the number of MHCII + cells in the injured hemisphere. These results suggest that intramuscular IGF-1 gene therapy may represent a new approach to prevent traumatic brain injury outcomes in rats.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/259677
url http://hdl.handle.net/10261/259677
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.brainresbull.2021.07.023
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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