Preeclampsia and Neurodevelopmental Outcomes: Potential Pathogenic Roles for Inflammation and Oxidative Stress?
Preeclampsia and Neurodevelopmental Outcomes: Potential Pathogenic Roles for Inflammation and Oxidative Stress?
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DOI：
10.1007/s12035-021-02290-4
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发表时间：
2021-01-25
影响因子：
5.1
通讯作者：
O'Keeffe, Gerard W.
中科院分区：
文献类型：
--
作者：
Barron, Aaron;McCarthy, Cathal M.;O'Keeffe, Gerard W.
先兆子痫（PE）是一种常见的严重妊娠期高血压疾病，发生在约3-5%的首次妊娠中，是众所周知的孕产妇和新生儿死亡和发病的主要原因。近年来，越来越多的证据表明，子宫内暴露于PE是各种神经发育障碍的环境风险因素，特别是自闭症谱系障碍和ADHD。目前，调节这种关系的机制尚不确定。在这篇综述中，我们概述了最新的证据表明，PE暴露在各种神经发育障碍的病因学的因果关系的作用，并提供了一种新的解释PE暴露后代的神经解剖学改变，以及这些如何与他们的次优神经发育轨迹。然后，我们假设炎症和氧化应激，PE的病理生理学的两个突出特征，可能在介导这种关联中发挥重要作用。PE中母体循环、胎盘和胎儿循环中的炎症增加使后代暴露于产前母体免疫激活（神经发育障碍的风险因素，已在动物模型中得到充分表征）和直接更高浓度的促炎细胞因子（对神经元发育产生不利影响）。类似地，母亲、胎盘和胎儿中过度的氧化应激诱导胎盘分泌对神经元有害的因子，并使胎儿脑暴露于直接升高的氧化应激，从而对神经发育过程产生不利影响。最后，我们描述了PE中炎症和氧化应激之间的相互作用，以及这两个系统如何相互作用，从而可能改变暴露后代的神经发育轨迹。
Preeclampsia (PE) is a common and serious hypertensive disorder of pregnancy that occurs in approximately 3-5% of first-time pregnancies and is a well-known leading cause of maternal and neonatal mortality and morbidity. In recent years, there has been accumulating evidence that in utero exposure to PE acts as an environmental risk factor for various neurodevelopmental disorders, particularly autism spectrum disorder and ADHD. At present, the mechanism(s) mediating this relationship are uncertain. In this review, we outline the most recent evidence implicating a causal role for PE exposure in the aetiology of various neurodevelopmental disorders and provide a novel interpretation of neuroanatomical alterations in PE-exposed offspring and how these relate to their sub-optimal neurodevelopmental trajectory. We then postulate that inflammation and oxidative stress, two prominent features of the pathophysiology of PE, are likely to play a major role in mediating this association. The increased inflammation in the maternal circulation, placenta and fetal circulation in PE expose the offspring to both prenatal maternal immune activation-a risk factor for neurodevelopmental disorders, which has been well-characterised in animal models-and directly higher concentrations of pro-inflammatory cytokines, which adversely affect neuronal development. Similarly, the exaggerated oxidative stress in the mother, placenta and foetus induces the placenta to secrete factors deleterious to neurons, and exposes the fetal brain to directly elevated oxidative stress and thus adversely affects neurodevelopmental processes. Finally, we describe the interplay between inflammation and oxidative stress in PE, and how both systems interact to potentially alter neurodevelopmental trajectory in exposed offspring.