Potentially toxic effects of anaesthetics on the developing central nervous system

E. Gascon, P. Klauser, J. Z. Kiss, L. Vutskits

Research output: Contribution to journalReview ArticleResearchpeer-review

14 Citations (Scopus)

Abstract

A growing body of experimental evidence suggests that anaesthetics, by influencing GABAergic and glutaminergic neural signalling, can have adverse effects on the developing central nervous system. The biological foundation for this is that gamma-aminobutyric acid and glutamate could act non-synaptically, in addition to their role in neurotransmission in the adult brain, in the regulation of neuronal development in the central nervous system. These neurotransmitters and their receptors are expressed from very early stages of central nervous system development and appear to influence neural progenitor proliferation, cell migration and neuronal differentiation. During the synaptogenetic period, pharmacological blockade of N-methyl-D-aspartate (NMDA)-type glutamate receptors as well as stimulation of GABAA receptors has been reported to be associated with increased apoptosis in the developing brain. Importantly, recent data suggest that even low, non-apoptogenic concentrations of anaesthetics can perturb neuronal dendritic development and thus could potentially lead to impairment of developing neuronal networks. The extrapolation of these experimental observations to clinical practice is of course very difficult and requires extreme caution as differences in drug concentrations and exposure times as well as interspecies variations are all important confounding variables. While clinicians should clearly not withhold anaesthesia based on current animal studies, these observations should urge more laboratory and clinical research to further elucidate this issue.

Original languageEnglish
Pages (from-to)213-224
Number of pages12
JournalEuropean Journal of Anaesthesiology
Volume24
Issue number3
DOIs
Publication statusPublished - 1 Mar 2007

Keywords

  • Anaesthesia
  • Anaesthetic agents
  • Apoptosis
  • Dendrites
  • Gamma-aminobutyric acid
  • Glutamate
  • Neurotoxicity

Cite this

@article{1884afdeb5c444658cab66ceb2e43a7d,
title = "Potentially toxic effects of anaesthetics on the developing central nervous system",
abstract = "A growing body of experimental evidence suggests that anaesthetics, by influencing GABAergic and glutaminergic neural signalling, can have adverse effects on the developing central nervous system. The biological foundation for this is that gamma-aminobutyric acid and glutamate could act non-synaptically, in addition to their role in neurotransmission in the adult brain, in the regulation of neuronal development in the central nervous system. These neurotransmitters and their receptors are expressed from very early stages of central nervous system development and appear to influence neural progenitor proliferation, cell migration and neuronal differentiation. During the synaptogenetic period, pharmacological blockade of N-methyl-D-aspartate (NMDA)-type glutamate receptors as well as stimulation of GABAA receptors has been reported to be associated with increased apoptosis in the developing brain. Importantly, recent data suggest that even low, non-apoptogenic concentrations of anaesthetics can perturb neuronal dendritic development and thus could potentially lead to impairment of developing neuronal networks. The extrapolation of these experimental observations to clinical practice is of course very difficult and requires extreme caution as differences in drug concentrations and exposure times as well as interspecies variations are all important confounding variables. While clinicians should clearly not withhold anaesthesia based on current animal studies, these observations should urge more laboratory and clinical research to further elucidate this issue.",
keywords = "Anaesthesia, Anaesthetic agents, Apoptosis, Dendrites, Gamma-aminobutyric acid, Glutamate, Neurotoxicity",
author = "E. Gascon and P. Klauser and Kiss, {J. Z.} and L. Vutskits",
year = "2007",
month = "3",
day = "1",
doi = "10.1017/S0265021506002365",
language = "English",
volume = "24",
pages = "213--224",
journal = "European Journal of Anaesthesiology",
issn = "0265-0215",
publisher = "Lippincott Williams & Wilkins",
number = "3",

}

Potentially toxic effects of anaesthetics on the developing central nervous system. / Gascon, E.; Klauser, P.; Kiss, J. Z.; Vutskits, L.

In: European Journal of Anaesthesiology, Vol. 24, No. 3, 01.03.2007, p. 213-224.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Potentially toxic effects of anaesthetics on the developing central nervous system

AU - Gascon, E.

AU - Klauser, P.

AU - Kiss, J. Z.

AU - Vutskits, L.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - A growing body of experimental evidence suggests that anaesthetics, by influencing GABAergic and glutaminergic neural signalling, can have adverse effects on the developing central nervous system. The biological foundation for this is that gamma-aminobutyric acid and glutamate could act non-synaptically, in addition to their role in neurotransmission in the adult brain, in the regulation of neuronal development in the central nervous system. These neurotransmitters and their receptors are expressed from very early stages of central nervous system development and appear to influence neural progenitor proliferation, cell migration and neuronal differentiation. During the synaptogenetic period, pharmacological blockade of N-methyl-D-aspartate (NMDA)-type glutamate receptors as well as stimulation of GABAA receptors has been reported to be associated with increased apoptosis in the developing brain. Importantly, recent data suggest that even low, non-apoptogenic concentrations of anaesthetics can perturb neuronal dendritic development and thus could potentially lead to impairment of developing neuronal networks. The extrapolation of these experimental observations to clinical practice is of course very difficult and requires extreme caution as differences in drug concentrations and exposure times as well as interspecies variations are all important confounding variables. While clinicians should clearly not withhold anaesthesia based on current animal studies, these observations should urge more laboratory and clinical research to further elucidate this issue.

AB - A growing body of experimental evidence suggests that anaesthetics, by influencing GABAergic and glutaminergic neural signalling, can have adverse effects on the developing central nervous system. The biological foundation for this is that gamma-aminobutyric acid and glutamate could act non-synaptically, in addition to their role in neurotransmission in the adult brain, in the regulation of neuronal development in the central nervous system. These neurotransmitters and their receptors are expressed from very early stages of central nervous system development and appear to influence neural progenitor proliferation, cell migration and neuronal differentiation. During the synaptogenetic period, pharmacological blockade of N-methyl-D-aspartate (NMDA)-type glutamate receptors as well as stimulation of GABAA receptors has been reported to be associated with increased apoptosis in the developing brain. Importantly, recent data suggest that even low, non-apoptogenic concentrations of anaesthetics can perturb neuronal dendritic development and thus could potentially lead to impairment of developing neuronal networks. The extrapolation of these experimental observations to clinical practice is of course very difficult and requires extreme caution as differences in drug concentrations and exposure times as well as interspecies variations are all important confounding variables. While clinicians should clearly not withhold anaesthesia based on current animal studies, these observations should urge more laboratory and clinical research to further elucidate this issue.

KW - Anaesthesia

KW - Anaesthetic agents

KW - Apoptosis

KW - Dendrites

KW - Gamma-aminobutyric acid

KW - Glutamate

KW - Neurotoxicity

UR - http://www.scopus.com/inward/record.url?scp=33846944295&partnerID=8YFLogxK

U2 - 10.1017/S0265021506002365

DO - 10.1017/S0265021506002365

M3 - Review Article

VL - 24

SP - 213

EP - 224

JO - European Journal of Anaesthesiology

JF - European Journal of Anaesthesiology

SN - 0265-0215

IS - 3

ER -