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Title

Differential neurotoxic effects of propofol on dissociated cortical cells and organotypic hippocampal cultures

Authors
Parisi, Lorena
Published in Anesthesiology. 2000, vol. 92, no. 5, p. 1408-1417
Abstract BACKGROUND: Propofol is a widely used anesthetic agent for adults and children. Although extensive clinical use has demonstrated its safety, neurologic dysfunctions have been described after the use of this agent. A recent study on a model of aggregating cell cultures reported that propofol might cause irreversible lesions of gamma-aminobutyric acid-mediated (GABAergic) neurons when administered at a critical phase of brain development. We investigated this issue by comparing the effects of long-term propofol treatment on two models of brain cultures: dissociated neonatal cortical cell cultures and organotypic slice cultures. METHODS: Survival of GABAergic neurons in dissociated cultures of newborn rat cortex (postnatal age, 1 day) treated for 3 days with different concentrations of propofol was assessed using histologic and cytochemical methods. For hippocampal organotypic slice cultures (postnatal age, 1 and 7 days), cell survival was assessed by measuring functional and morphologic parameters: extracellular and intracellular electrophysiology, propidium staining of dying cells, and light and electron microscopy. RESULTS: In dissociated neonatal cell cultures, propofol induced dose-dependent lesions of GABAergic neurons and of glial cells. In contrast, no evidence for neurotoxic effects of propofol were found after long-term treatment of organotypic slice cultures. Excitatory transmission was not affected by propofol, and inhibitory transmission was still functional. Histologic preparations showed no evidence for cell degeneration or death. CONCLUSION: Although long-term applications of propofol to dissociated cortical cell cultures produced degeneration and death of GABAergic neurons and glial cells, no such lesions were found when using a model of postnatal organotypic slice cultures. This conclusion is based on both functional and morphologic tests.
Keywords Anesthetics, Intravenous/ toxicityAnimalsAnimals, NewbornCell Death/drug effectsCells, CulturedCerebral Cortex/cytology/ drug effects/physiologyCulture TechniquesDose-Response Relationship, DrugElectrophysiologyHippocampus/cytology/ drug effects/physiologyMembrane Potentials/drug effectsNeurons/cytology/drug effectsPatch-Clamp TechniquesPropofol/ toxicityRatsRats, Sprague-DawleyReceptors, GABA-A/drug effects
Stable URL http://archive-ouverte.unige.ch/unige:10450
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PMID: 10781288
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