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

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 mam...

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Autores principales: Maksimovic, Stefan, Useinovic, Nemanja, Quillinan, Nidia, Covey, Douglas F., Todorovic, Slobodan M., Jevtovic-Todorovic, Vesna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836828/
https://www.ncbi.nlm.nih.gov/pubmed/35163810
http://dx.doi.org/10.3390/ijms23031889
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author Maksimovic, Stefan
Useinovic, Nemanja
Quillinan, Nidia
Covey, Douglas F.
Todorovic, Slobodan M.
Jevtovic-Todorovic, Vesna
author_facet Maksimovic, Stefan
Useinovic, Nemanja
Quillinan, Nidia
Covey, Douglas F.
Todorovic, Slobodan M.
Jevtovic-Todorovic, Vesna
author_sort Maksimovic, Stefan
collection PubMed
description 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.
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spelling pubmed-88368282022-02-12 General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action Maksimovic, Stefan Useinovic, Nemanja Quillinan, Nidia Covey, Douglas F. Todorovic, Slobodan M. Jevtovic-Todorovic, Vesna Int J Mol Sci Review 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. MDPI 2022-02-08 /pmc/articles/PMC8836828/ /pubmed/35163810 http://dx.doi.org/10.3390/ijms23031889 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Maksimovic, Stefan
Useinovic, Nemanja
Quillinan, Nidia
Covey, Douglas F.
Todorovic, Slobodan M.
Jevtovic-Todorovic, Vesna
General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action
title General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action
title_full General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action
title_fullStr General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action
title_full_unstemmed General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action
title_short General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action
title_sort general anesthesia and the young brain: the importance of novel strategies with alternate mechanisms of action
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836828/
https://www.ncbi.nlm.nih.gov/pubmed/35163810
http://dx.doi.org/10.3390/ijms23031889
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