Brites Dora, Fernandes Adelaide
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
Semin Fetal Neonatal Med. 2015 Feb;20(1):14-19. doi: 10.1016/j.siny.2014.12.002. Epub 2014 Dec 19.
Bilirubin-induced neurologic dysfunction (BIND) and classical kernicterus are clinical manifestations of moderate to severe hyperbilirubinemia whenever bilirubin levels exceed the capacity of the brain defensive mechanisms in preventing its entrance and cytotoxicity. In such circumstances and depending on the associated co-morbidities, bilirubin accumulation may lead to short- or long-term neurodevelopmental disabilities, which may include deficits in auditory, cognitive, and motor processing. Neuronal cell death, astrocytic reactivity, and microglia activation are part of the bilirubin-induced pathogenesis. Less understood is how abnormal growth and maturation of oligodendrocytes may impact on brain development, affecting the formation of myelin tracts. Based on in-vitro and in-vivo models, as well as in clinical cases presented here, we propose the existence of impaired myelination by bilirubin with long-term sequelae, mainly in pre-term infants. Sensitive time-windows are highlighted and centered on the different developmental-dependent impairments determined by bilirubin, and the influence of sepsis and hypoxia is reviewed.
胆红素诱导的神经功能障碍（BIND）和经典核黄疸是中度至重度高胆红素血症的临床表现，只要胆红素水平超过大脑防御机制阻止其进入和细胞毒性的能力。在这种情况下，根据相关的合并症，胆红素积累可能导致短期或长期的神经发育障碍，这可能包括听觉、认知和运动处理方面的缺陷。神经元细胞死亡、星形胶质细胞反应和小胶质细胞激活是胆红素诱导的发病机制的一部分。少为人知的是少突胶质细胞的异常生长和成熟如何影响大脑发育，影响髓鞘束的形成。基于体外和体内模型以及本文介绍的临床病例，我们提出胆红素导致髓鞘形成受损并伴有长期后遗症，主要发生在早产儿中。文中强调了敏感时间窗，并围绕胆红素所确定的不同发育依赖性损伤展开，同时还综述了败血症和缺氧的影响。
