Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.

<h4>Aim</h4>We have previously shown that lithium treatment immediately after hypoxia-ischemia (HI) in neonatal rats affords both short- and long-term neuroprotection. The aim of this study was to evaluate possible therapeutic benefits when lithium treatment was delayed 5 days, a time po...

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Autores principales:	Cuicui Xie, Kai Zhou, Xiaoyang Wang, Klas Blomgren, Changlian Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a5baafcfe8fa4c82a52bcc715a7b3c56
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spelling	oai:doaj.org-article:a5baafcfe8fa4c82a52bcc715a7b3c562021-11-25T06:00:57ZTherapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.1932-620310.1371/journal.pone.0107192https://doaj.org/article/a5baafcfe8fa4c82a52bcc715a7b3c562014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107192https://doaj.org/toc/1932-6203<h4>Aim</h4>We have previously shown that lithium treatment immediately after hypoxia-ischemia (HI) in neonatal rats affords both short- and long-term neuroprotection. The aim of this study was to evaluate possible therapeutic benefits when lithium treatment was delayed 5 days, a time point when most cell death is over.<h4>Methods</h4>Eight-day-old male rats were subjected to unilateral HI and 2 mmol/kg lithium chloride was injected intraperitoneally 5 days after the insult. Additional lithium injections of 1 mmol/kg were administered at 24 h intervals for the next 14 days. Brain injury was evaluated 12 weeks after HI. Serum cytokine measurements and behavioral analysis were performed before sacrificing the animals.<h4>Results</h4>Brain injury, as indicated by tissue loss, was reduced by 38.7%, from 276.5±27.4 mm3 in the vehicle-treated group to 169.3±25.9 mm3 in the lithium-treated group 12 weeks after HI (p<0.01). Motor hyperactivity and anxiety-like behavior after HI were normalized by lithium treatment. Lithium treatment increased neurogenesis in the dentate gyrus as indicated by doublecortin labeling. Serum cytokine levels, including IL-1α, IL-1β, and IL-6, were still elevated as late as 5 weeks after HI, but lithium treatment normalized these cytokine levels.<h4>Conclusions</h4>Delayed lithium treatment conferred long-term neuroprotection in neonatal rats after HI, and this opens a new avenue for future development of treatment strategies for neonatal brain injury that can be administered after the acute injury phase.Cuicui XieKai ZhouXiaoyang WangKlas BlomgrenChanglian ZhuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107192 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cuicui Xie Kai Zhou Xiaoyang Wang Klas Blomgren Changlian Zhu Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
description	<h4>Aim</h4>We have previously shown that lithium treatment immediately after hypoxia-ischemia (HI) in neonatal rats affords both short- and long-term neuroprotection. The aim of this study was to evaluate possible therapeutic benefits when lithium treatment was delayed 5 days, a time point when most cell death is over.<h4>Methods</h4>Eight-day-old male rats were subjected to unilateral HI and 2 mmol/kg lithium chloride was injected intraperitoneally 5 days after the insult. Additional lithium injections of 1 mmol/kg were administered at 24 h intervals for the next 14 days. Brain injury was evaluated 12 weeks after HI. Serum cytokine measurements and behavioral analysis were performed before sacrificing the animals.<h4>Results</h4>Brain injury, as indicated by tissue loss, was reduced by 38.7%, from 276.5±27.4 mm3 in the vehicle-treated group to 169.3±25.9 mm3 in the lithium-treated group 12 weeks after HI (p<0.01). Motor hyperactivity and anxiety-like behavior after HI were normalized by lithium treatment. Lithium treatment increased neurogenesis in the dentate gyrus as indicated by doublecortin labeling. Serum cytokine levels, including IL-1α, IL-1β, and IL-6, were still elevated as late as 5 weeks after HI, but lithium treatment normalized these cytokine levels.<h4>Conclusions</h4>Delayed lithium treatment conferred long-term neuroprotection in neonatal rats after HI, and this opens a new avenue for future development of treatment strategies for neonatal brain injury that can be administered after the acute injury phase.
format	article
author	Cuicui Xie Kai Zhou Xiaoyang Wang Klas Blomgren Changlian Zhu
author_facet	Cuicui Xie Kai Zhou Xiaoyang Wang Klas Blomgren Changlian Zhu
author_sort	Cuicui Xie
title	Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
title_short	Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
title_full	Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
title_fullStr	Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
title_full_unstemmed	Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
title_sort	therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a5baafcfe8fa4c82a52bcc715a7b3c56
work_keys_str_mv	AT cuicuixie therapeuticbenefitsofdelayedlithiumadministrationintheneonatalrataftercerebralhypoxiaischemia AT kaizhou therapeuticbenefitsofdelayedlithiumadministrationintheneonatalrataftercerebralhypoxiaischemia AT xiaoyangwang therapeuticbenefitsofdelayedlithiumadministrationintheneonatalrataftercerebralhypoxiaischemia AT klasblomgren therapeuticbenefitsofdelayedlithiumadministrationintheneonatalrataftercerebralhypoxiaischemia AT changlianzhu therapeuticbenefitsofdelayedlithiumadministrationintheneonatalrataftercerebralhypoxiaischemia
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Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.

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