The anti-inflammatory compound candesartan cilexetil improves neurological outcomes in a mouse model of neonatal hypoxia

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dc.contributor.authorQuinlan, Sean
dc.contributor.authorMerino-Serrais, Paula
dc.contributor.authorDi Grande, Alessandra
dc.contributor.authorDussmann, Heiko
dc.contributor.authorPrehn, Jochen H. M.
dc.contributor.authorNí Chonghaile, Tríona
dc.contributor.authorHenshall, David C.
dc.contributor.authorJimenez-Mateos, Eva M.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEuropean Regional Development Funden
dc.contributor.funderFutureNeuroen
dc.contributor.funderSvenska Sällskapet för Medicinsk Forskningen
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidadesen
dc.date.accessioned2019-12-10T11:52:52Z
dc.date.available2019-12-10T11:52:52Z
dc.date.issued2019-07-24
dc.description.abstractRecent studies suggest that mild hypoxia-induced neonatal seizures can trigger an acute neuroinflammatory response leading to long-lasting changes in brain excitability along with associated cognitive and behavioral deficits. The cellular elements and signaling pathways underlying neuroinflammation in this setting remain incompletely understood but could yield novel therapeutic targets. Here we show that brief global hypoxia-induced neonatal seizures in mice result in transient cytokine production, a selective expansion of microglia and long-lasting changes to the neuronal structure of pyramidal neurons in the hippocampus. Treatment of neonatal mice after hypoxia-seizures with the novel anti-inflammatory compound candesartan cilexetil suppressed acute seizure-damage and mitigated later-life aggravated seizure responses and hippocampus-dependent learning deficits. Together, these findings improve our understanding of the effects of neonatal seizures and identify potentially novel treatments to protect against short and long-lasting harmful effects.en
dc.description.sponsorshipScience Foundation Ireland (16/RC/3948)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid1752en
dc.identifier.citationQuinlan, S., Merino-Serrais, P., Di Grande, A., Dussmann, H., Prehn, J. H. M., Ní Chonghaile, T., Henshall, D. C. and Jimenez-Mateos, E. M. (2019) 'The Anti-inflammatory Compound Candesartan Cilexetil Improves Neurological Outcomes in a Mouse Model of Neonatal Hypoxia', Frontiers in Immunology, 10, 1752 (15pp). doi: 10.3389/fimmu.2019.01752en
dc.identifier.doi10.3389/fimmu.2019.01752en
dc.identifier.eissn1664-3224
dc.identifier.endpage15en
dc.identifier.journaltitleFrontiers in immunologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9379
dc.identifier.volume10en
dc.language.isoenen
dc.publisherFrontiers Mediaen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Starting Investigator Research Grant (SIRG)/13/SIRG/2114/IE/microRNA in the pathogenesis and prognosis of neonatal brain injury/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2272/IE/Irish Centre for Fetal and Neonatal Translational Research (INFANT)/en
dc.rights© 2019, Quinlan, Merino-Serrais, Di Grande, Dussmann, Prehn, Ní Chonghaile, Henshall and Jimenez-Mateos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectNeonatal encephalopathyen
dc.subjectInflammationen
dc.subjectMicrogliaen
dc.subjectSeizuresen
dc.subjectHypoxiaen
dc.titleThe anti-inflammatory compound candesartan cilexetil improves neurological outcomes in a mouse model of neonatal hypoxiaen
dc.typeArticle (peer-reviewed)en
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