Molecular Mechanisms of Anesthetic Neurotoxicity: A Review of the Current Literature.
Molecular Mechanisms of Anesthetic Neurotoxicity: A Review of the Current Literature.
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DOI：
10.1097/ana.0000000000000348
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发表时间：
2016-10
影响因子：
3.7
通讯作者：
Mintz CD
中科院分区：
文献类型：
--
作者：
Jackson WM;Gray CD;Jiang D;Schaefer ML;Connor C;Mintz CD
来自流行病学研究和动物模型的数据引起了人们的担忧，即出生后早期接触麻醉剂可能会导致认知功能的持久损害。据推测，这是由于大脑发育中断所致，但这种毒性效应背后的机制尚不清楚。正在进行的研究，特别是在啮齿动物身上的研究，已经开始解决这个问题。本文从细胞死亡途径、生长因子信号系统、NMDA和GABA受体、线粒体和表观遗传因子等方面探讨了目前推测的麻醉剂在脑发育过程中毒性的分子机制。对每一种假定机制的证据水平进行了严格的评估，我们试图在可能的情况下将它们之间的联系联系起来。虽然有许多有希望的研究途径，但目前还不能就损伤的确切机制达成共识。
Data from epidemiologic studies and animal models have raised a concern that exposure to anesthetic agents during early postnatal life may cause lasting impairments in cognitive function. It is hypothesized that this is due to disruptions in brain development, but the mechanism underlying this toxic effect remains unknown. Ongoing research, particularly in rodents, has begun to address this question. In this review we examine currently postulated molecular mechanisms of anesthetic toxicity in the developing brain, including effects on cell death pathways, growth factor signaling systems, NMDA and GABA receptors, mitochondria, and epigenetic factors. The level of evidence for each putative mechanism is critically evaluated, and we attempt to draw connections between them where it is possible to do so. While there are many promising avenues of research, at this time no consensus can be reached as to a definitive mechanism of injury.