Bilirubin-induced immunostimulant effects and toxicity vary with neural cell type and maturation state
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- 作者：Ana S. Falc?o ; Adelaide Fernandes ; Maria A. Brito ; Rui F. M. Silva and Dora Brites
- 关键词：Astrocytes ; Cell maturation ; Cell reactivity ; Neurons ; Unconjugated bilirubin
- 刊名：Acta Neuropathologica
- 出版年：2006
- 出版时间：July 2006
- 年：2006
- 卷：112
- 期：1
- 页码：95-105
- 全文大小：421 KB
文摘
Hyperbilirubinemia remains one of the most frequent clinical diagnoses in the neonatal period. The increased vulnerability of premature infants to unconjugated bilirubin (UCB)-induced brain damage may be due to a proneness of immature nerve cells to UCB-toxic stimulus. Thus, in this study, we evaluated UCB-induced cell death, glutamate release and cytokine production, in astrocytes and neurons cultured for different days, in order to relate the differentiation state with cell vulnerability to UCB. The age-dependent activation of the nuclear factor-κB (NF-κB), an important transcription factor involved in inflammation, was also investigated. Furthermore, responsiveness of neurons and astrocytes to UCB were compared in order to identify the most susceptible to each induced effect, as an approach to what happens in vivo. The results clearly showed that immature nerve cells are more vulnerable than the most differentiated ones to UCB-induced cell death, glutamate release and tumour necrosis factor (TNF)-α secretion. Moreover, astrocytes seem to be more competent cells in releasing glutamate and in producing an inflammatory response when injured by UCB. Activation of NF-κB by UCB also presents a cell-age-dependent pattern, and values vary with neural cell type. Again, astrocytes have the highest activation levels, which are correlated with the greater amount of cytokine production observed in these cells. These results contribute to a better knowledge of the mechanisms leading to UCB encephalopathy by elucidation of age- and type-related differences in neural cell responses to UCB.