Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells

Unconjugated bilirubin (UCB) encephalopathy is a predominantly early life condition resulting from the impairment of several cellular functions in the brain of severely jaundiced infants. However, only few data exist on the age-dependent effects of UCB and their association with increased vulnerabil...

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Main Authors: Ana S. Falcão, Adelaide Fernandes, Maria A. Brito, Rui F.M. Silva, Dora Brites
Format: Article
Language:English
Published: Elsevier 2005-11-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S096999610500077X
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spelling doaj-f3759531313a4a208a8b88a5ae35f0802021-03-20T04:51:09ZengElsevierNeurobiology of Disease1095-953X2005-11-01202199206Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cellsAna S. Falcão0Adelaide Fernandes1Maria A. Brito2Rui F.M. Silva3Dora Brites4Centro de Patogénese Molecular (UBMBE), Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisboa, PortugalCentro de Patogénese Molecular (UBMBE), Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisboa, PortugalCentro de Patogénese Molecular (UBMBE), Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisboa, PortugalCentro de Patogénese Molecular (UBMBE), Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisboa, PortugalCorresponding author. Fax: +351 21 7946491.; Centro de Patogénese Molecular (UBMBE), Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisboa, PortugalUnconjugated bilirubin (UCB) encephalopathy is a predominantly early life condition resulting from the impairment of several cellular functions in the brain of severely jaundiced infants. However, only few data exist on the age-dependent effects of UCB and their association with increased vulnerability of premature newborns, particularly in a sepsis condition. We investigated cell death, glutamate efflux, and inflammatory cytokine dynamics after exposure of astrocytes at different stages of differentiation to clinically relevant concentrations of UCB and/or lipopolysaccharide (LPS). Younger astrocytes were more prone to UCB-induced cell death, glutamate efflux, and inflammatory response than older ones. Furthermore, in immature cells, LPS exacerbated UCB effects, such as cell death by necrosis. These findings provide a basis for the increased susceptibility of premature newborns to UCB deleterious effects, namely when associated with sepsis, and underline how crucial the course of cell maturation can be to UCB encephalopathy during moderate to severe neonatal jaundice.http://www.sciencedirect.com/science/article/pii/S096999610500077XAstrocytesDevelopmentCell deathGlutamate releaseLipopolysaccharide (LPS)Cytokines
collection DOAJ
language English
format Article
sources DOAJ
author Ana S. Falcão
Adelaide Fernandes
Maria A. Brito
Rui F.M. Silva
Dora Brites
spellingShingle Ana S. Falcão
Adelaide Fernandes
Maria A. Brito
Rui F.M. Silva
Dora Brites
Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
Neurobiology of Disease
Astrocytes
Development
Cell death
Glutamate release
Lipopolysaccharide (LPS)
Cytokines
author_facet Ana S. Falcão
Adelaide Fernandes
Maria A. Brito
Rui F.M. Silva
Dora Brites
author_sort Ana S. Falcão
title Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
title_short Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
title_full Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
title_fullStr Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
title_full_unstemmed Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
title_sort bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2005-11-01
description Unconjugated bilirubin (UCB) encephalopathy is a predominantly early life condition resulting from the impairment of several cellular functions in the brain of severely jaundiced infants. However, only few data exist on the age-dependent effects of UCB and their association with increased vulnerability of premature newborns, particularly in a sepsis condition. We investigated cell death, glutamate efflux, and inflammatory cytokine dynamics after exposure of astrocytes at different stages of differentiation to clinically relevant concentrations of UCB and/or lipopolysaccharide (LPS). Younger astrocytes were more prone to UCB-induced cell death, glutamate efflux, and inflammatory response than older ones. Furthermore, in immature cells, LPS exacerbated UCB effects, such as cell death by necrosis. These findings provide a basis for the increased susceptibility of premature newborns to UCB deleterious effects, namely when associated with sepsis, and underline how crucial the course of cell maturation can be to UCB encephalopathy during moderate to severe neonatal jaundice.
topic Astrocytes
Development
Cell death
Glutamate release
Lipopolysaccharide (LPS)
Cytokines
url http://www.sciencedirect.com/science/article/pii/S096999610500077X
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