During fetal development, cerebral cortical neurons are generated in the proliferative zone along the ventricles and then migrate to their final positions. To examine the impact of in utero exposure to anesthetics on neuronal migration, we injected pregnant rats with bromodeoxyuridine to label fetal neurons generated at embryonic Day (E) 17 and then randomized these rats to 9 different groups receiving 3 different means of anesthesia (oxygen/control, propofol, isoflurane) for 3 exposure durations (20, 50, 120 min). Histological analysis of brains from 54 pups revealed that significant number of neurons in anesthetized animals failed to acquire their correct cortical position and remained dispersed within inappropriate cortical layers and/or adjacent white matter. Behavioral testing of 86 littermates pointed to abnormalities that correspond to the aberrations in the brain areas that are specifically developing during the E17. In the second set of experiments, fetal brains exposed to isoflurane at E16 had diminished expression of the reelin and glutamic acid decarboxylase 67, proteins critical for neuronal migration. Together, these results call for cautious use of anesthetics during the neuronal migration period in pregnancy and more comprehensive investigation of neurodevelopmental consequences for the fetus and possible consequences later in life.

中文翻译：

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子宫内麻醉剂暴露会改变发育中的大脑皮层的神经元迁移模式，并导致大鼠产后行为缺陷。

在胎儿发育过程中，大脑皮层神经元在沿着脑室的增生区中产生，然后迁移到它们的最终位置。为了检查子宫内麻醉药对神经元迁移的影响，我们给孕鼠注射了溴脱氧尿苷，以标记在胚胎第（E）17天产生的胎儿神经元，然后将这些鼠随机分为9个不同的组，分别接受3种不同的麻醉方式（氧气/对照，异丙酚，异氟烷）暴露3次（20、50、120分钟）。对来自54只幼崽的大脑进行的组织学分析表明，麻醉动物中大量神经元无法获得正确的皮质位置，并且仍然分散在不适当的皮质层和/或相邻的白质中。对86个同窝仔的行为测试指出，异常与E17期间特别发展的大脑区域的畸变相对应。在第二组实验中，在E16暴露于异氟烷的胎儿大脑减少了对神经元迁移至关重要的蛋白质reelin和谷氨酸脱羧酶67的表达。总之，这些结果要求在孕妇的神经元迁移期间谨慎使用麻醉剂，并更全面地调查对胎儿的神经发育后果以及生命后期可能产生的后果。对神经元迁移至关重要的蛋白质。总之，这些结果要求在怀孕的神经元迁移期间谨慎使用麻醉剂，并更全面地调查对胎儿的神经发育后果以及生命后期可能产生的后果。对神经元迁移至关重要的蛋白质。总之，这些结果要求在怀孕的神经元迁移期间谨慎使用麻醉剂，并更全面地调查对胎儿的神经发育后果以及生命后期可能产生的后果。