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dc.contributor.authorQueiroga, CSF
dc.contributor.authorTomasi, Simone
dc.contributor.authorWiderøe, Marius
dc.contributor.authorAlves, Paula M.
dc.contributor.authorVercelli, A.
dc.contributor.authorVieira, Helena LA
dc.date.accessioned2015-10-30T11:38:43Z
dc.date.accessioned2015-11-26T09:27:08Z
dc.date.available2015-10-30T11:38:43Z
dc.date.available2015-11-26T09:27:08Z
dc.date.issued2012
dc.identifier.citationPLoS ONE 2012, 7(8)nb_NO
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11250/2365818
dc.description.abstractPerinatal hypoxia-ischemia is a major cause of acute mortality in newborns and cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play a major role. Increased resistance against major damage can be achieved by preconditioning triggered by subtle insults. CO, a toxic molecule that is also generated endogenously, may have a role in preconditioning as low doses can protect against inflammation and apoptosis. In this study, the role of CO-induced preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h of CO treatment on neuronal death (plasmatic membrane permeabilization and chromatin condensation) and bcl-2 expression was studied in cerebellar granule cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were counted with a stereological approach and cleaved caspase 3-positive profiles in the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c released from mitochondria and reduced activation of caspase-3. Still, Bcl-2 protein levels were higher in hippocampus of CO pre-treated rat pups. Our results show that CO preconditioning elicits a molecular cascade that limits neuronal apoptosis. This could represent an innovative therapeutic strategy for high-risk cerebral hypoxia-ischemia patients, in particular neonates.nb_NO
dc.language.isoengnb_NO
dc.publisherPublic Library of Sciencenb_NO
dc.titlePreconditioning Triggered by Carbon Monoxide (CO) Provides Neuronal Protection Following Perinatal Hypoxia-Ischemianb_NO
dc.typeJournal articlenb_NO
dc.typePeer revieweden_GB
dc.date.updated2015-10-30T11:38:43Z
dc.source.volume7nb_NO
dc.source.journalPLoS ONEnb_NO
dc.source.issue8nb_NO
dc.identifier.doi10.1371/journal.pone.0042632
dc.identifier.cristin963491
dc.description.localcode© Queiroga et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.nb_NO


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