Bilirubin-induced immunostimulant effects and toxicity vary with neural cell type and maturation state
Bilirubin-induced immunostimulant effects and toxicity vary with neural cell type and maturation state
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DOI：
10.1007/s00401-006-0078-4
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发表时间：
2006-07-01
影响因子：
12.7
通讯作者：
Brites, Dora
中科院分区：
文献类型：
--
作者：
Falcao, Ana S.;Fernandes, Adelaide;Brites, Dora
高胆红素血症仍然是新生儿期最常见的临床诊断之一。早产儿对非共轭胆红素（UCB）诱导的脑损伤的易感性增加可能是由于未成熟神经细胞对UCB毒性刺激的倾向。因此，在本研究中，我们对培养不同天数的星形胶质细胞和神经元中UCB诱导的细胞死亡、谷氨酸释放和细胞因子产生进行了评估，以便将分化状态与细胞对UCB的易感性联系起来。研究人员还研究了核因子κ B （nf - κ B）的年龄依赖性激活，nf - κ B是一种重要的炎症转录因子。此外，我们还比较了神经元和星形胶质细胞对UCB的反应性，以确定最容易受到每种诱导效应的影响，从而了解体内发生的情况。结果清楚地表明，未成熟神经细胞比分化程度最高的神经细胞更容易受到ucb诱导的细胞死亡、谷氨酸释放和肿瘤坏死因子(TNF)- α分泌的影响。此外，星形胶质细胞似乎在UCB损伤时更能释放谷氨酸并产生炎症反应。UCB对NF-kappa B的激活也呈现细胞年龄依赖模式，其值随神经细胞类型而变化。同样，星形胶质细胞具有最高的激活水平，这与在这些细胞中观察到的大量细胞因子产生相关。这些结果有助于更好地了解导致UCB脑病的机制，通过阐明年龄和类型相关的神经细胞对UCB的反应差异。
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-kappa B (NF-kappa B), 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)-alpha 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-kappa B 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.