dc.contributor.author | Queiroga, CSF | |
dc.contributor.author | Tomasi, Simone | |
dc.contributor.author | Widerøe, Marius | |
dc.contributor.author | Alves, Paula M. | |
dc.contributor.author | Vercelli, A. | |
dc.contributor.author | Vieira, Helena LA | |
dc.date.accessioned | 2015-10-30T11:38:43Z | |
dc.date.accessioned | 2015-11-26T09:27:08Z | |
dc.date.available | 2015-10-30T11:38:43Z | |
dc.date.available | 2015-11-26T09:27:08Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | PLoS ONE 2012, 7(8) | nb_NO |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/11250/2365818 | |
dc.description.abstract | Perinatal 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.iso | eng | nb_NO |
dc.publisher | Public Library of Science | nb_NO |
dc.title | Preconditioning Triggered by Carbon Monoxide (CO) Provides Neuronal Protection Following Perinatal Hypoxia-Ischemia | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | en_GB |
dc.date.updated | 2015-10-30T11:38:43Z | |
dc.source.volume | 7 | nb_NO |
dc.source.journal | PLoS ONE | nb_NO |
dc.source.issue | 8 | nb_NO |
dc.identifier.doi | 10.1371/journal.pone.0042632 | |
dc.identifier.cristin | 963491 | |
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 |