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我们是否有可行的策略来预防麻醉诱导的发育性神经毒性?

Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?

机构信息

Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Neuronal Injury and Plasticity Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

出版信息

Int J Mol Sci. 2022 Jan 20;23(3):1128. doi: 10.3390/ijms23031128.

Abstract

Since its invention, general anesthesia has been an indispensable component of modern surgery. While traditionally considered safe and beneficial in many pathological settings, hundreds of preclinical studies in various animal species have raised concerns about the detrimental and long-lasting consequences that general anesthetics may cause to the developing brain. Clinical evidence of anesthetic neurotoxicity in humans continues to mount as we continue to contemplate how to move forward. Notwithstanding the alarming evidence, millions of children are being anesthetized each year, setting the stage for substantial healthcare burdens in the future. Hence, furthering our knowledge of the molecular underpinnings of anesthesia-induced developmental neurotoxicity is crucially important and should enable us to develop protective strategies so that currently available general anesthetics could be safely used during critical stages of brain development. In this mini-review, we provide a summary of select strategies with primary focus on the mechanisms of neuroprotection and potential for clinical applicability. First, we summarize a diverse group of chemicals with the emphasis on intracellular targets and signal-transduction pathways. We then discuss epigenetic and transgenerational effects of general anesthetics and potential remedies, and also anesthesia-sparing or anesthesia-delaying approaches. Finally, we present evidence of a novel class of anesthetics with a distinct mechanism of action and a promising safety profile.

摘要

自发明以来,全身麻醉一直是现代外科手术不可或缺的组成部分。虽然在许多病理情况下,全身麻醉被传统认为是安全且有益的,但各种动物物种的数百项临床前研究引起了人们对全身麻醉可能对发育中的大脑造成的有害和持久影响的担忧。随着我们继续思考如何前进,麻醉神经毒性的临床证据不断增加。尽管有令人震惊的证据,但每年仍有数百万儿童接受麻醉,这为未来带来了巨大的医疗保健负担。因此,深入了解麻醉诱导的发育性神经毒性的分子基础至关重要,这将使我们能够制定保护策略,以便在大脑发育的关键阶段安全使用目前可用的全身麻醉剂。在这篇小型综述中,我们提供了一些选择策略的摘要,主要侧重于神经保护的机制和临床应用的潜力。首先,我们总结了一组具有不同作用机制的化学物质,重点是细胞内靶标和信号转导途径。然后,我们讨论了全身麻醉的表观遗传和跨代效应及其潜在的补救措施,以及减少或延迟麻醉的方法。最后,我们提出了一类具有独特作用机制和良好安全性的新型麻醉剂的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3998/8834847/d4766f035ee4/ijms-23-01128-g001.jpg

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