Kang Eunchai, Berg Daniel A, Furmanski Orion, Jackson William M, Ryu Yun Kyoung, Gray Christy D, Mintz C David
Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Anesthesiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neurotoxicol Teratol. 2017 Mar-Apr;60:33-39. doi: 10.1016/j.ntt.2016.10.001. Epub 2016 Oct 14.
The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure. Intriguingly, neurogenesis is a major developmental event that occurs during postulated windows of vulnerability to developmental anesthetic neurotoxicity across the different species in which it has been studied. In this review, we examine the evidence for anesthetic effects on neurogenesis in the early postnatal period and ask whether neurogenesis should be studied further as a putative mechanism of injury. Multiple anesthetics are considered, and both in vivo and in vitro work is presented. While there is abundant evidence that anesthetics act to suppress neurogenesis at several different phases, evidence of a causal link between these effects and any change in learning behavior remains elusive.
麻醉剂作用于发育中的大脑从而导致长期缺陷的机制仍未完全明确。海马体被认为是一个可能涉及其中的结构,因为啮齿动物模型显示在依赖海马体的学习行为任务中存在众多缺陷。海马体是一个特殊的结构,因为它是出生后大量神经发生的部位,尤其是在人类生命的第一年,这些新生成的神经元对该结构的功能至关重要。有趣的是,神经发生是一个主要的发育事件,发生在不同物种假定的易受发育性麻醉神经毒性影响的窗口期内,而这些物种都已被研究过。在这篇综述中,我们研究了出生后早期麻醉剂对神经发生影响的证据,并探讨神经发生是否应作为一种假定的损伤机制进行进一步研究。我们考虑了多种麻醉剂,并展示了体内和体外研究工作。虽然有大量证据表明麻醉剂在几个不同阶段抑制神经发生,但这些影响与学习行为的任何变化之间的因果关系证据仍然难以捉摸。