Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.

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...

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Autores principales:	Cláudia S F Queiroga, Simone Tomasi, Marius Widerøe, Paula M Alves, Alessandro Vercelli, Helena L A Vieira
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f24a17968855478fad5cf716ded0a8fe
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spelling	oai:doaj.org-article:f24a17968855478fad5cf716ded0a8fe2021-11-18T07:07:23ZPreconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.1932-620310.1371/journal.pone.0042632https://doaj.org/article/f24a17968855478fad5cf716ded0a8fe2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952602/?tool=EBIhttps://doaj.org/toc/1932-6203Perinatal 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.Cláudia S F QueirogaSimone TomasiMarius WiderøePaula M AlvesAlessandro VercelliHelena L A VieiraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42632 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cláudia S F Queiroga Simone Tomasi Marius Widerøe Paula M Alves Alessandro Vercelli Helena L A Vieira Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.
description	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.
format	article
author	Cláudia S F Queiroga Simone Tomasi Marius Widerøe Paula M Alves Alessandro Vercelli Helena L A Vieira
author_facet	Cláudia S F Queiroga Simone Tomasi Marius Widerøe Paula M Alves Alessandro Vercelli Helena L A Vieira
author_sort	Cláudia S F Queiroga
title	Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.
title_short	Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.
title_full	Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.
title_fullStr	Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.
title_full_unstemmed	Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.
title_sort	preconditioning triggered by carbon monoxide (co) provides neuronal protection following perinatal hypoxia-ischemia.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f24a17968855478fad5cf716ded0a8fe
work_keys_str_mv	AT claudiasfqueiroga preconditioningtriggeredbycarbonmonoxidecoprovidesneuronalprotectionfollowingperinatalhypoxiaischemia AT simonetomasi preconditioningtriggeredbycarbonmonoxidecoprovidesneuronalprotectionfollowingperinatalhypoxiaischemia AT mariuswiderøe preconditioningtriggeredbycarbonmonoxidecoprovidesneuronalprotectionfollowingperinatalhypoxiaischemia AT paulamalves preconditioningtriggeredbycarbonmonoxidecoprovidesneuronalprotectionfollowingperinatalhypoxiaischemia AT alessandrovercelli preconditioningtriggeredbycarbonmonoxidecoprovidesneuronalprotectionfollowingperinatalhypoxiaischemia AT helenalavieira preconditioningtriggeredbycarbonmonoxidecoprovidesneuronalprotectionfollowingperinatalhypoxiaischemia
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Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.

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