Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells
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DOI：
10.1016/j.nbd.2005.03.001
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Brites, D
中科院分区：
文献类型：
--
作者：
Falcao, AS;Fernandes, A;Brites, D
未结合胆红素（UCB）脑病是一种主要的早期生活条件造成的损害，在严重黄疸的婴儿大脑中的几个细胞功能。然而，只有很少的数据存在的年龄依赖性的影响，脐带血和他们的关联增加的脆弱性早产儿，特别是在败血症的条件。我们研究了细胞死亡，谷氨酸外流，并在不同分化阶段的星形胶质细胞暴露于临床相关浓度的UCB和/或脂多糖（LPS）后的炎症细胞因子动力学。年轻的星形胶质细胞比年长的星形胶质细胞更容易发生UCB诱导的细胞死亡、谷氨酸流出和炎症反应。此外，在未成熟细胞中，LPS加剧了UCB效应，如坏死导致的细胞死亡。这些发现为早产儿对UCB有害作用的易感性增加提供了依据，即与脓毒症相关时，并强调了细胞成熟过程在中度至重度新生儿黄疸期间对UCB脑病的重要性。(c)2005年爱思唯尔公司All rights reserved.
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. (c) 2005 Elsevier Inc. All rights reserved.