Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment.,Neurobiology of Learning and Memory

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Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment.
Neurobiology of Learning and Memory ( IF 2.2 ) Pub Date : 2018-03-14 , DOI: 10.1016/j.nlm.2018.03.014
Susan E Maloney ₁ , Catherine E Creeley ₂ , Richard E Hartman ₃ , Carla M Yuede ₄ , Charles F Zorumski ₅ , Vesna Jevtovic-Todorovic ₆ , Krikor Dikranian ₇ , Kevin K Noguchi ₁ , Nuri B Farber ₁ , David F Wozniak ₈

Affiliation

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Intellectual and Developmental Disabilities Research Center, Washington University, St. Louis, MO, USA.
Department of Psychology, The State University of New York at Fredonia, Fredonia, NY 14063, USA.
Department of Psychology, Loma Linda University, 11130 Anderson St., Loma Linda, CA 92354, USA.
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA.
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA.
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA; Intellectual and Developmental Disabilities Research Center, Washington University, St. Louis, MO, USA.

Fifteen years ago Olney and colleagues began using animal models to evaluate the effects of anesthetic and sedative agents (ASAs) on neurodevelopment. The results from ongoing studies indicate that, under certain conditions, exposure to these drugs during development induces an acute elevated apoptotic neurodegenerative response in the brain and long-term functional impairments. These animal models have played a significant role in bringing attention to the possible adverse effects of exposing the developing brain to ASAs when few concerns had been raised previously in the medical community. The apoptotic degenerative response resulting from neonatal exposure to ASAs has been replicated in many studies in both rodents and non-human primates, suggesting that a similar effect may occur in humans. In both rodents and non-human primates, significantly increased levels of apoptotic degeneration are often associated with functional impairments later in life. However, behavioral deficits following developmental ASA exposure have not been consistently reported even when significantly elevated levels of apoptotic degeneration have been documented in animal models. In the present work, we review this literature and propose a rodent model for assessing potential functional deficits following neonatal ASA exposure with special reference to experimental design and procedural issues. Our intent is to improve test sensitivity and replicability for detecting subtle behavioral effects, and thus enhance the translational significance of ASA models.

中文翻译：

使用动物模型评估早期神经发育过程中麻醉的功能后果。

十五年前，奥尔尼和同事开始使用动物模型来评估麻醉和镇静剂 (ASA) 对神经发育的影响。正在进行的研究结果表明，在某些条件下，在发育过程中接触这些药物会引起大脑中细胞凋亡神经退行性反应的急性升高和长期功能障碍。这些动物模型在引起人们对将发育中的大脑暴露于 ASA 可能产生的不利影响方面发挥了重要作用，而此前医学界对此几乎没有提出任何担忧。新生儿接触 ASA 导致的细胞凋亡退行性反应已在啮齿类动物和非人类灵长类动物的许多研究中得到重复，这表明类似的效应也可能发生在人类身上。在啮齿动物和非人类灵长类动物中，细胞凋亡变性水平的显着增加通常与晚年的功能障碍有关。然而，即使在动物模型中记录了细胞凋亡变性水平显着升高，但发育期 ASA 暴露后的行为缺陷尚未得到一致报道。在目前的工作中，我们回顾了这些文献，并提出了一种啮齿动物模型，用于评估新生儿 ASA 暴露后潜在的功能缺陷，特别参考实验设计和程序问题。我们的目的是提高检测微妙行为效应的测试灵敏度和可重复性，从而增强 ASA 模型的转化意义。

更新日期：2018-03-14

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