Anesthetics interfere with the polarization of developing cortical neurons

Cyrus David Mintz, Sarah C. Smith, Kendall M S Barrett, Deanna L. Benson

Research output: Contribution to journalArticle

Abstract

Abstract: Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also seems to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABA A receptors. Rather, the delay in axon specification likely results from a slowing of the extension of prepolarized neurites. The effect is not unique to isoflurane as propofol also seems to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere with brain development through effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.

Original languageEnglish (US)
Pages (from-to)368-375
Number of pages8
JournalJournal of Neurosurgical Anesthesiology
Volume24
Issue number4
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Anesthetics
Axons
Isoflurane
Neurons
Propofol
General Anesthetics
Poisons
Brain
Neurites
GABA-A Receptors
Dendrites
Synapses
Cell Survival
Cell Death
Pediatrics
Growth

Keywords

  • anesthetic
  • axon
  • isoflurane
  • neuron
  • neurotoxicity
  • polarity

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Clinical Neurology
  • Surgery

Cite this

Anesthetics interfere with the polarization of developing cortical neurons. / Mintz, Cyrus David; Smith, Sarah C.; Barrett, Kendall M S; Benson, Deanna L.

In: Journal of Neurosurgical Anesthesiology, Vol. 24, No. 4, 10.2012, p. 368-375.

Research output: Contribution to journalArticle

Mintz, Cyrus David ; Smith, Sarah C. ; Barrett, Kendall M S ; Benson, Deanna L. / Anesthetics interfere with the polarization of developing cortical neurons. In: Journal of Neurosurgical Anesthesiology. 2012 ; Vol. 24, No. 4. pp. 368-375.
@article{0b07b9607f5a402cad0e56e50c349fb3,
title = "Anesthetics interfere with the polarization of developing cortical neurons",
abstract = "Abstract: Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also seems to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABA A receptors. Rather, the delay in axon specification likely results from a slowing of the extension of prepolarized neurites. The effect is not unique to isoflurane as propofol also seems to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere with brain development through effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.",
keywords = "anesthetic, axon, isoflurane, neuron, neurotoxicity, polarity",
author = "Mintz, {Cyrus David} and Smith, {Sarah C.} and Barrett, {Kendall M S} and Benson, {Deanna L.}",
year = "2012",
month = "10",
doi = "10.1097/ANA.0b013e31826a03a6",
language = "English (US)",
volume = "24",
pages = "368--375",
journal = "Journal of Neurosurgical Anesthesiology",
issn = "0898-4921",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Anesthetics interfere with the polarization of developing cortical neurons

AU - Mintz, Cyrus David

AU - Smith, Sarah C.

AU - Barrett, Kendall M S

AU - Benson, Deanna L.

PY - 2012/10

Y1 - 2012/10

N2 - Abstract: Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also seems to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABA A receptors. Rather, the delay in axon specification likely results from a slowing of the extension of prepolarized neurites. The effect is not unique to isoflurane as propofol also seems to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere with brain development through effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.

AB - Abstract: Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also seems to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABA A receptors. Rather, the delay in axon specification likely results from a slowing of the extension of prepolarized neurites. The effect is not unique to isoflurane as propofol also seems to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere with brain development through effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.

KW - anesthetic

KW - axon

KW - isoflurane

KW - neuron

KW - neurotoxicity

KW - polarity

UR - http://www.scopus.com/inward/record.url?scp=84866427457&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866427457&partnerID=8YFLogxK

U2 - 10.1097/ANA.0b013e31826a03a6

DO - 10.1097/ANA.0b013e31826a03a6

M3 - Article

C2 - 23085784

AN - SCOPUS:84866427457

VL - 24

SP - 368

EP - 375

JO - Journal of Neurosurgical Anesthesiology

JF - Journal of Neurosurgical Anesthesiology

SN - 0898-4921

IS - 4

ER -