General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action

International Journal of Molecular Sciences

Slobodan M. Todorovic¹  Nidia Quillinan¹  Vesna Jevtovic-Todorovic¹  Stefan Maksimovic¹  Nemanja Useinovic¹  Douglas F. Covey² 

[1] Department of Anesthesiology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA;Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA;

关键词: general anesthetics;    neurotoxicity;    neuroactive steroid analogues;    synaptogenesis;   

DOI  :  10.3390/ijms23031889

来源: DOAJ

【 摘 要 】

Over the past three decades, we have been grappling with rapidly accumulating evidence that general anesthetics (GAs) may not be as innocuous for the young brain as we previously believed. The growing realization comes from hundreds of animal studies in numerous species, from nematodes to higher mammals. These studies argue that early exposure to commonly used GAs causes widespread apoptotic neurodegeneration in brain regions critical to cognition and socio-emotional development, kills a substantial number of neurons in the young brain, and, importantly, results in lasting disturbances in neuronal synaptic communication within the remaining neuronal networks. Notably, these outcomes are often associated with long-term impairments in multiple cognitive-affective domains. Not only do preclinical studies clearly demonstrate GA-induced neurotoxicity when the exposures occur in early life, but there is a growing body of clinical literature reporting similar cognitive-affective abnormalities in young children who require GAs. The need to consider alternative GAs led us to focus on synthetic neuroactive steroid analogues that have emerged as effective hypnotics, and analgesics that are apparently devoid of neurotoxic effects and long-term cognitive impairments. This would suggest that certain steroid analogues with different cellular targets and mechanisms of action may be safe alternatives to currently used GAs. Herein we summarize our current knowledge of neuroactive steroids as promising novel GAs.

【 授权许可】

Unknown