Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures.

Details

Serval ID
serval:BIB_68F5B67016CC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures.
Journal
Journal of Neuroscience Research
Author(s)
Honegger P., Matthieu J.M.
ISSN
0360-4012 (Print)
ISSN-L
0360-4012
Publication state
Published
Issued date
1996
Volume
45
Number
5
Pages
631-636
Language
english
Abstract
The intravenous, short-acting general anesthetic propofol was applied to three-dimensional (aggregating) cell cultures of fetal rat telencephalon. Both the clinically used formulation (Disoprivan, ICI Pharmaceuticals, Cheshire, England) and the pure form (2,6-diisopropylphenol) were tested at two different periods of brain development: immature brain cell cultures prior to synaptogenesis and at the time of intense synapses and myelin formation. At both time periods and for clinically relevant concentrations and time of exposure (i.e., concentrations > or = 2.0 micrograms/ml for 8 hr), propofol caused a significant decrease of glutamic acid decarboxylase activity. This effect persisted after removal of the drug, suggesting irreversible structural changes in GABAergic neurons. The gamma-aminobutyric acid type A (GABAA) blocking agents bicuculline and picrotoxin partially attenuated the neurotoxic effect of propofol in cultures treated at the more mature phase of development. This protective effect was not observed in the immature brain cells. The present data suggest that propofol may cause irreversible lesions to GABAergic neurons when given at a critical phase of brain development. In contrast, glial cells and myelin appeared resistant even to high doses of propofol.
Keywords
Anesthetics, General/toxicity, Animals, Cells, Cultured, DNA/metabolism, Glutamate Decarboxylase/metabolism, Myelin Basic Protein/metabolism, Nerve Tissue Proteins/metabolism, Neurons/drug effects, Neurons/enzymology, Parasympathetic Nervous System/cytology, Parasympathetic Nervous System/drug effects, Propofol/toxicity, Rats, Telencephalon/cytology, Telencephalon/enzymology, gamma-Aminobutyric Acid/physiology
Pubmed
Web of science
Create date
24/01/2008 14:12
Last modification date
20/08/2019 15:24
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