The evolving landscape of neurotoxicity by unconjugated bilirubin: role of glial cells and inflammation.
The evolving landscape of neurotoxicity by unconjugated bilirubin: role of glial cells and inflammation.
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DOI：
10.3389/fphar.2012.00088
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发表时间：
2012
影响因子：
5.6
通讯作者：
Brites D
中科院分区：
文献类型：
--
作者：
Brites D
未结合的高胆红素血症是一种常见的条件，在出生后的第一周。虽然一般来说是无害的，但一些新生儿可能会产生非常高水平的未结合胆红素（UCB），这可能超过大脑在防止UCB积累方面的保护机制。在这种情况下，可能会产生短期和长期的神经发育障碍，如急性和慢性UCB脑病，称为核黄疸，或更细微的改变，如胆红素诱导的神经功能障碍（BIND）。由于尚未解释的原因，婴儿对UCB的易感性存在巨大的差异，但早产、败血症、缺氧和溶血性疾病被认为是危险因素。因此，UCB水平与神经异常没有严格的相关性。即使在今天，UCB神经毒性的机制仍然不清楚，特定的生物标志物也不清楚，而且对高胆红素血症引起的持久后遗症知之甚少。尸检显示，UCB位于神经元、神经元突和小胶质细胞内，并导致神经元丢失、脱髓鞘和胶质细胞增生。在分离的细胞培养中，UCB被证明可以损害神经元树突，并诱导小胶质细胞和星形胶质细胞释放促炎细胞因子。然而，细胞依赖性对UCB毒性的敏感性和每种神经细胞类型的作用仍未完全了解。本文综述了UCB在神经元、星形胶质细胞和少突胶质细胞中的细胞敏感性和分子靶点，以及小胶质细胞对UCB的表型和功能反应。强调了胶质细胞元件之间的相互作用和与神经元的串扰，特别强调了ucb诱导的免疫刺激，以及脓毒症在BIND发病机制中的作用。关于不同药物的抗炎和抗氧化活性的新和有趣的数据也被提出，作为新的和有前途的额外治疗方法。
Unconjugated hyperbilirubinemia is a common condition in the first week of postnatal life. Although generally harmless, some neonates may develop very high levels of unconjugated bilirubin (UCB), which may surpass the protective mechanisms of the brain in preventing UCB accumulation. In this case, both short-term and long-term neurodevelopmental disabilities, such as acute and chronic UCB encephalopathy, known as kernicterus, or more subtle alterations defined as bilirubin-induced neurological dysfunction (BIND) may be produced. There is a tremendous variability in babies’ vulnerability toward UCB for reasons not yet explained, but preterm birth, sepsis, hypoxia, and hemolytic disease are comprised as risk factors. Therefore, UCB levels and neurological abnormalities are not strictly correlated. Even nowadays, the mechanisms of UCB neurotoxicity are still unclear, as are specific biomarkers, and little is known about lasting sequelae attributable to hyperbilirubinemia. On autopsy, UCB was shown to be within neurons, neuronal processes, and microglia, and to produce loss of neurons, demyelination, and gliosis. In isolated cell cultures, UCB was shown to impair neuronal arborization and to induce the release of pro-inflammatory cytokines from microglia and astrocytes. However, cell dependent sensitivity to UCB toxicity and the role of each nerve cell type remains not fully understood. This review provides a comprehensive insight into cell susceptibilities and molecular targets of UCB in neurons, astrocytes, and oligodendrocytes, and on phenotypic and functional responses of microglia to UCB. Interplay among glia elements and cross-talk with neurons, with a special emphasis in the UCB-induced immunostimulation, and the role of sepsis in BIND pathogenesis are highlighted. New and interesting data on the anti-inflammatory and antioxidant activities of different pharmacological agents are also presented, as novel and promising additional therapeutic approaches to BIND.
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影响因子：
12.7
作者：
Bradl M;Lassmann H
通讯作者：
Lassmann H
影响因子：
2.9
作者：
Brito, MA;Brites, D;Butterfield, DA
通讯作者：
Butterfield, DA
影响因子：
6.1
作者：
Brito, MA;Silva, RFM;Brites, D
通讯作者：
Brites, D
影响因子：
8
作者：
Bhutani, Vinod K.
通讯作者：
Bhutani, Vinod K.
发育和病理过程中的脑血管生成：中风后神经血管损伤和血管生成恢复。
DOI：
10.1111/j.1742-4658.2009.07176.x
发表时间：
2009-09
期刊：
The FEBS journal
影响因子：
--
作者：
Arai K;Jin G;Navaratna D;Lo EH
通讯作者：
Lo EH