Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation

Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to...

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Autores: Reyes-Corral, Marta, Gil-González, Laura, González-Díaz, Ángela, Tovar-Luzón, Javier, Ayuso, María Irene, Lao-Pérez, Miguel, Montaner, Joan, Puerta, Rocío de la, Fernández-Torres, Rut, Ybot, Patricia
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/387002
Acesso em linha:http://hdl.handle.net/10261/387002
https://api.elsevier.com/content/abstract/scopus_id/85201628197
Access Level:acceso abierto
Palavra-chave:Microglia
Neonatal hypoxia-ischemia
Neuroprotection
Oleuropein
White matter injury
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spelling Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammationReyes-Corral, MartaGil-González, LauraGonzález-Díaz, ÁngelaTovar-Luzón, JavierAyuso, María IreneLao-Pérez, MiguelMontaner, JoanPuerta, Rocío de laFernández-Torres, RutYbot, PatriciaMicrogliaNeonatal hypoxia-ischemiaNeuroprotectionOleuropeinWhite matter injuryHypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.This work was supported by the following funding bodies: (1) Consejería de Transformación Económica, Industria, Conocimiento y Universidades; Junta de Andalucía [DOC_01701 to M.R.-C., P20_01267 to P.Y.-G.]. (2) Consejería de Salud y Bienestar Social; Junta de Andalucía [RH-0033-2020 to M.R.-C., C-0025-2018 to P.Y.-G.]. (3) Instituto de Salud Carlos III (ISCIII), co-funded by the European Union [PI20/00769 to P.Y.-G.]. (4) Fundación Alicia Koplowitz [“Ayudas a proyectos de investigación en neuropediatría 2018” to J.M.].Peer reviewedSage PublicationsJunta de AndalucíaInstituto de Salud Carlos IIIEuropean CommissionFundación Alicia KoplowitzReyes-Corral, Marta [0000-0002-5490-0624]Montaner, Joan [0000-0003-4845-2279]Ybot, Patricia [0000-0001-7836-2659]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/387002https://api.elsevier.com/content/abstract/scopus_id/85201628197reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolismhttps://doi.org/10.1177/0271678X241270237Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3870022026-05-22T06:33:51Z
dc.title.none.fl_str_mv Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
title Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
spellingShingle Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
Reyes-Corral, Marta
Microglia
Neonatal hypoxia-ischemia
Neuroprotection
Oleuropein
White matter injury
title_short Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
title_full Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
title_fullStr Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
title_full_unstemmed Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
title_sort Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation
dc.creator.none.fl_str_mv Reyes-Corral, Marta
Gil-González, Laura
González-Díaz, Ángela
Tovar-Luzón, Javier
Ayuso, María Irene
Lao-Pérez, Miguel
Montaner, Joan
Puerta, Rocío de la
Fernández-Torres, Rut
Ybot, Patricia
author Reyes-Corral, Marta
author_facet Reyes-Corral, Marta
Gil-González, Laura
González-Díaz, Ángela
Tovar-Luzón, Javier
Ayuso, María Irene
Lao-Pérez, Miguel
Montaner, Joan
Puerta, Rocío de la
Fernández-Torres, Rut
Ybot, Patricia
author_role author
author2 Gil-González, Laura
González-Díaz, Ángela
Tovar-Luzón, Javier
Ayuso, María Irene
Lao-Pérez, Miguel
Montaner, Joan
Puerta, Rocío de la
Fernández-Torres, Rut
Ybot, Patricia
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Junta de Andalucía
Instituto de Salud Carlos III
European Commission
Fundación Alicia Koplowitz
Reyes-Corral, Marta [0000-0002-5490-0624]
Montaner, Joan [0000-0003-4845-2279]
Ybot, Patricia [0000-0001-7836-2659]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Microglia
Neonatal hypoxia-ischemia
Neuroprotection
Oleuropein
White matter injury
topic Microglia
Neonatal hypoxia-ischemia
Neuroprotection
Oleuropein
White matter injury
description Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
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/10261/387002
https://api.elsevier.com/content/abstract/scopus_id/85201628197
url http://hdl.handle.net/10261/387002
https://api.elsevier.com/content/abstract/scopus_id/85201628197
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
https://doi.org/10.1177/0271678X241270237
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Sage Publications
publisher.none.fl_str_mv Sage Publications
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 15,81155

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