Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex

Autores
Chang, Eileen I.; Zárate, Miguel A.; Rabaglino, Maria Belen; Richards, Elaine M.; Arndt, Thomas J.; Keller Wood, Maureen; Wood, Charles E.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.
Fil: Chang, Eileen I.. University of Florida; Estados Unidos
Fil: Zárate, Miguel A.. University of Florida; Estados Unidos
Fil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina
Fil: Richards, Elaine M.. University of Florida; Estados Unidos
Fil: Arndt, Thomas J.. University of Florida; Estados Unidos
Fil: Keller Wood, Maureen. University of Florida; Estados Unidos
Fil: Wood, Charles E.. University of Florida; Estados Unidos
Materia
FETAL HYPOXIA
FRONTAL CORTEX
IMMUNE RESPONSE
KETAMINE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/180065
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortexChang, Eileen I.Zárate, Miguel A.Rabaglino, Maria BelenRichards, Elaine M.Arndt, Thomas J.Keller Wood, MaureenWood, Charles E.FETAL HYPOXIAFRONTAL CORTEXIMMUNE RESPONSEKETAMINEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zárate, Miguel A.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados UnidosWiley Blackwell Publishing, Inc2016-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/180065Chang, Eileen I.; Zárate, Miguel A.; Rabaglino, Maria Belen; Richards, Elaine M.; Arndt, Thomas J.; et al.; Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex; Wiley Blackwell Publishing, Inc; Physiological Reports; 4; 6; 3-2016; 1-152051-817XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.12741info:eu-repo/semantics/altIdentifier/doi/10.14814/phy2.12741info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:36Zoai:ri.conicet.gov.ar:11336/180065instacron: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:34982025-09-29 09:32:36.338CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
title Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
spellingShingle Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
Chang, Eileen I.
FETAL HYPOXIA
FRONTAL CORTEX
IMMUNE RESPONSE
KETAMINE
title_short Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
title_full Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
title_fullStr Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
title_full_unstemmed Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
title_sort Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex
dc.creator.none.fl_str_mv Chang, Eileen I.
Zárate, Miguel A.
Rabaglino, Maria Belen
Richards, Elaine M.
Arndt, Thomas J.
Keller Wood, Maureen
Wood, Charles E.
author Chang, Eileen I.
author_facet Chang, Eileen I.
Zárate, Miguel A.
Rabaglino, Maria Belen
Richards, Elaine M.
Arndt, Thomas J.
Keller Wood, Maureen
Wood, Charles E.
author_role author
author2 Zárate, Miguel A.
Rabaglino, Maria Belen
Richards, Elaine M.
Arndt, Thomas J.
Keller Wood, Maureen
Wood, Charles E.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FETAL HYPOXIA
FRONTAL CORTEX
IMMUNE RESPONSE
KETAMINE
topic FETAL HYPOXIA
FRONTAL CORTEX
IMMUNE RESPONSE
KETAMINE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.
Fil: Chang, Eileen I.. University of Florida; Estados Unidos
Fil: Zárate, Miguel A.. University of Florida; Estados Unidos
Fil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina
Fil: Richards, Elaine M.. University of Florida; Estados Unidos
Fil: Arndt, Thomas J.. University of Florida; Estados Unidos
Fil: Keller Wood, Maureen. University of Florida; Estados Unidos
Fil: Wood, Charles E.. University of Florida; Estados Unidos
description Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.
publishDate 2016
dc.date.none.fl_str_mv 2016-03
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/11336/180065
Chang, Eileen I.; Zárate, Miguel A.; Rabaglino, Maria Belen; Richards, Elaine M.; Arndt, Thomas J.; et al.; Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex; Wiley Blackwell Publishing, Inc; Physiological Reports; 4; 6; 3-2016; 1-15
2051-817X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/180065
identifier_str_mv Chang, Eileen I.; Zárate, Miguel A.; Rabaglino, Maria Belen; Richards, Elaine M.; Arndt, Thomas J.; et al.; Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex; Wiley Blackwell Publishing, Inc; Physiological Reports; 4; 6; 3-2016; 1-15
2051-817X
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://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.12741
info:eu-repo/semantics/altIdentifier/doi/10.14814/phy2.12741
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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
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score 13.070432

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