

Other version: http://journals.lww.com/anesthesiology/Fulltext/2000/05000/Differential_Neurotoxic_Effects_of_Propofol_on.32.aspx
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Differential neurotoxic effects of propofol on dissociated cortical cells and organotypic hippocampal cultures |
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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/ toxicity — Animals — Animals, Newborn — Cell Death/drug effects — Cells, Cultured — Cerebral Cortex/cytology/ drug effects/physiology — Culture Techniques — Dose-Response Relationship, Drug — Electrophysiology — Hippocampus/cytology/ drug effects/physiology — Membrane Potentials/drug effects — Neurons/cytology/drug effects — Patch-Clamp Techniques — Propofol/ toxicity — Rats — Rats, Sprague-Dawley — Receptors, GABA-A/drug effects | |
Identifiers | PMID: 10781288 | |
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![]() ![]() Other version: http://journals.lww.com/anesthesiology/Fulltext/2000/05000/Differential_Neurotoxic_Effects_of_Propofol_on.32.aspx |
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Citation (ISO format) | SPAHR-SCHOPFER, Isabelle et al. Differential neurotoxic effects of propofol on dissociated cortical cells and organotypic hippocampal cultures. In: Anesthesiology, 2000, vol. 92, n° 5, p. 1408-1417. doi: 10.1097/00000542-200005000-00032 https://archive-ouverte.unige.ch/unige:10450 |