Brito Maria Alexandra, Palmela Inês, Cardoso Filipa Lourenço, Sá-Pereira Inês, Brites Dora
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.
Arch Med Res. 2014 Nov;45(8):660-76. doi: 10.1016/j.arcmed.2014.11.015. Epub 2014 Dec 1.
The blood-brain barrier (BBB) is a complex and dynamic structure that plays a key role in central nervous system (CNS) homeostasis. It strictly regulates the entrance of molecules into the brain parenchyma and prevents the access of neurotoxins and pathogens while promoting the efflux of several molecules. The brain microvascular endothelial cells are the anatomical basis of the BBB, which has unique characteristics such as the elaborate junctional complexes that nearly obliterate the intercellular space as well as the presence of influx and efflux transporters. Endothelial cells establish important interactions with glial cells, neurons, and perivascular pericytes as well as with the acellular components of the basement membrane, which together constitute the neurovascular unit. BBB disruption has been reported in a wide range of CNS pathologies, with an emerging role in the onset and disease progression. Accordingly, recent studies revealed vascular dysfunction in neonatal jaundice, a common pathology in the early neonatal period affecting 1/10 children presenting values of total bilirubin>17 mg/dL (291 μM). Here we summarize the clinical aspects of moderate to severe neonatal jaundice and provide a comprehensive review of the literature regarding bilirubin-induced neurotoxicity from a vascular-centered approach. The collected evidence place endothelial dysfunction and pericyte demise as key players in the disruption of CNS homeostasis, mainly in cases of lasting hyperbilirubinemia, thus pointing to novel targets to prevent neurological dysfunction due to severe neonatal jaundice.
血脑屏障（BBB）是一种复杂且动态的结构，在中枢神经系统（CNS）稳态中起关键作用。它严格调节分子进入脑实质的过程，防止神经毒素和病原体进入，同时促进多种分子的外流。脑微血管内皮细胞是血脑屏障的解剖学基础，具有独特的特征，如精细的连接复合体几乎消除了细胞间空间，以及存在流入和流出转运体。内皮细胞与神经胶质细胞、神经元、血管周围周细胞以及基底膜的无细胞成分建立重要的相互作用，这些共同构成了神经血管单元。在多种中枢神经系统疾病中均有血脑屏障破坏的报道，其在疾病的发生和进展中发挥着越来越重要的作用。因此，最近的研究揭示了新生儿黄疸中的血管功能障碍，新生儿黄疸是新生儿早期的一种常见病症，每10名总胆红素值>17 mg/dL（291 μM）的儿童中就有1例受其影响。在此，我们总结了中度至重度新生儿黄疸的临床情况，并从以血管为中心的角度对胆红素诱导的神经毒性的相关文献进行了全面综述。收集到的证据表明，内皮功能障碍和周细胞死亡是破坏中枢神经系统稳态的关键因素，主要发生在持续性高胆红素血症的情况下，从而为预防严重新生儿黄疸所致神经功能障碍指明了新的靶点。
