Complex spectrum of phenobarbital effects in a mouse model of neonatal hypoxia-induced seizures

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dc.contributor.author Quinlan, Sean M. M.
dc.contributor.author Rodriguez-Alvarez, Natalia
dc.contributor.author Molloy, Eleanor J.
dc.contributor.author Madden, Stephen F.
dc.contributor.author Boylan, Geraldine B.
dc.contributor.author Henshall, David C.
dc.contributor.author Jimenez-Mateos, Eva M.
dc.date.accessioned 2018-08-29T15:47:26Z
dc.date.available 2018-08-29T15:47:26Z
dc.date.issued 2018
dc.identifier.citation Quinlan, S. M. M., Rodriguez-Alvarez, N., Molloy, E. J., Madden, S. F., Boylan, G. B., Henshall, D. C. and Jimenez-Mateos, E. M. (2018) 'Complex spectrum of phenobarbital effects in a mouse model of neonatal hypoxia-induced seizures', Scientific Reports, 8(1), 9986 (12pp). doi: 10.1038/s41598-018-28044-2 en
dc.identifier.volume 8
dc.identifier.startpage 1
dc.identifier.endpage 12
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10468/6674
dc.identifier.doi 10.1038/s41598-018-28044-2
dc.description.abstract Seizures in neonates, mainly caused by hypoxic-ischemic encephalopathy, are thought to be harmful to the brain. Phenobarbital remains the first line drug therapy for the treatment of suspected neonatal seizures but concerns remain with efficacy and safety. Here we explored the short- and long-term outcomes of phenobarbital treatment in a mouse model of hypoxia-induced neonatal seizures. Seizures were induced in P7 mice by exposure to 5% O-2 for 15 minutes. Immediately after hypoxia, pups received a single dose of phenobarbital (25 mg.kg(-1)) or saline. We observed that after administration of phenobarbital seizure burden and number of seizures were reduced compared to the hypoxic period; however, PhB did not suppress acute histopathology. Behavioural analysis of mice at 5 weeks of age previously subjected to hypoxia-seizures revealed an increase in anxiety-like behaviour and impaired memory function compared to control littermates, and these effects were not normalized by phenobarbital. In a seizure susceptibility test, pups previously exposed to hypoxia, with or without phenobarbital, developed longer and more severe seizures in response to kainic acid injection compared to control mice. Unexpectedly, mice treated with phenobarbital developed less hippocampal damage after kainic acid than untreated counterparts. The present study suggests phenobarbital treatment in immature mice does not improve the long lasting functional deficits induces by hypoxia-induced seizures but, unexpectedly, may reduce neuronal death caused by exposure to a second seizure event in later life. en
dc.description.sponsorship Health Research Board (HRA_POR/2012/56) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Nature Publishing Group en
dc.relation.uri https://www.nature.com/articles/s41598-018-28044-2
dc.rights © 2018, the Authors. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject Antiepileptic drugs en
dc.subject Febrile seizures en
dc.subject Neuronal injury en
dc.subject P2x7 receptor en
dc.subject Cell-death en
dc.subject Rat brain en
dc.subject Exposure en
dc.subject Mice en
dc.subject Susceptibility en
dc.subject Pathogenesis en
dc.title Complex spectrum of phenobarbital effects in a mouse model of neonatal hypoxia-induced seizures en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Geraldine Boylan, Medicine , University College Cork, Cork, Ireland. +353-21-490-3000 Email: g.boylan@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Health Research Board
dc.contributor.funder Science Foundation Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle Scientific Reports en
dc.internal.IRISemailaddress g.boylan@ucc.ie en
dc.identifier.articleid 9986
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2272/IE/Irish Centre for Fetal and Neonatal Translational Research (INFANT)/
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Advance Award Programme/14/ADV/RC2721/IE/Bioinformatics and predictive analytics for the identification of microRNA biomarkers of neonatal seizures/
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Starting Investigator Research Grant (SIRG)/13/SIRG/2114/IE/microRNA in the pathogenesis and prognosis of neonatal brain injury/


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© 2018, the Authors. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Except where otherwise noted, this item's license is described as © 2018, the Authors. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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