Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep

Autores
Chang, Eileen I.; Zarate, Miguel A.; Arndt, Thomas J.; Richards, Elaine M.; Rabaglino, Maria Belen; Keller Wood, Maureen; Wood, Charles E.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.
Fil: Chang, Eileen I.. University of Florida; Estados Unidos
Fil: Zarate, Miguel A.. University of Florida; Estados Unidos
Fil: Arndt, Thomas J.. University of Florida; Estados Unidos
Fil: Richards, Elaine M.. University of Florida; Estados Unidos
Fil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Keller Wood, Maureen. University of Florida; Estados Unidos
Fil: Wood, Charles E.. University of Florida; Estados Unidos
Materia
FETAL BRAIN
FETAL HYPOXIA
INFLAMMATION
KETAMINE
TRANSCRIPTOMICS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/124793
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheepChang, Eileen I.Zarate, Miguel A.Arndt, Thomas J.Richards, Elaine M.Rabaglino, Maria BelenKeller Wood, MaureenWood, Charles E.FETAL BRAINFETAL HYPOXIAINFLAMMATIONKETAMINETRANSCRIPTOMICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zarate, Miguel A.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados UnidosFrontiers Media S.A.2019-01-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/124793Chang, Eileen I.; Zarate, Miguel A.; Arndt, Thomas J.; Richards, Elaine M.; Rabaglino, Maria Belen; et al.; Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep; Frontiers Media S.A.; Frontiers in Physiology; 10; JAN; 7-1-20191664-042XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fphys.2018.01858/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fphys.2018.01858info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:31Zoai:ri.conicet.gov.ar:11336/124793instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:49:31.995CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
title Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
spellingShingle Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
Chang, Eileen I.
FETAL BRAIN
FETAL HYPOXIA
INFLAMMATION
KETAMINE
TRANSCRIPTOMICS
title_short Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
title_full Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
title_fullStr Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
title_full_unstemmed Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
title_sort Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep
dc.creator.none.fl_str_mv Chang, Eileen I.
Zarate, Miguel A.
Arndt, Thomas J.
Richards, Elaine M.
Rabaglino, Maria Belen
Keller Wood, Maureen
Wood, Charles E.
author Chang, Eileen I.
author_facet Chang, Eileen I.
Zarate, Miguel A.
Arndt, Thomas J.
Richards, Elaine M.
Rabaglino, Maria Belen
Keller Wood, Maureen
Wood, Charles E.
author_role author
author2 Zarate, Miguel A.
Arndt, Thomas J.
Richards, Elaine M.
Rabaglino, Maria Belen
Keller Wood, Maureen
Wood, Charles E.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FETAL BRAIN
FETAL HYPOXIA
INFLAMMATION
KETAMINE
TRANSCRIPTOMICS
topic FETAL BRAIN
FETAL HYPOXIA
INFLAMMATION
KETAMINE
TRANSCRIPTOMICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.
Fil: Chang, Eileen I.. University of Florida; Estados Unidos
Fil: Zarate, Miguel A.. University of Florida; Estados Unidos
Fil: Arndt, Thomas J.. University of Florida; Estados Unidos
Fil: Richards, Elaine M.. University of Florida; Estados Unidos
Fil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: Keller Wood, Maureen. University of Florida; Estados Unidos
Fil: Wood, Charles E.. University of Florida; Estados Unidos
description The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.
publishDate 2019
dc.date.none.fl_str_mv 2019-01-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/124793
Chang, Eileen I.; Zarate, Miguel A.; Arndt, Thomas J.; Richards, Elaine M.; Rabaglino, Maria Belen; et al.; Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep; Frontiers Media S.A.; Frontiers in Physiology; 10; JAN; 7-1-2019
1664-042X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/124793
identifier_str_mv Chang, Eileen I.; Zarate, Miguel A.; Arndt, Thomas J.; Richards, Elaine M.; Rabaglino, Maria Belen; et al.; Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep; Frontiers Media S.A.; Frontiers in Physiology; 10; JAN; 7-1-2019
1664-042X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fphys.2018.01858/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fphys.2018.01858
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268978421956608
score 13.13397

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