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 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.
Falcão
Ana S
AS
Centro de Patogénese Molecular (UBMBE), Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisboa, Portugal.
Fernandes
Adelaide
A
Brito
Maria A
MA
Silva
Rui F M
RF
Brites
Dora
D
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001663:Bilirubin / Q000378:metabolism / Q000633:toxicity; D015984:Causality; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004660:Encephalitis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism / Q000633:toxicity; D007647:Kernicterus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D047928:Premature Birth / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018698:Glutamic Acid; D001663:Bilirubin