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Published on: December 20, 2011
Propofol induces growth cone collapse and neurite retractions in chick explant culture
Wael S Al-Jahdari1, Shigeru Saito, Takashi Nakano
1Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-city, Gunma, 371-8511, Japan.
Purpose:
Propofol neurotoxicity has been demonstrated in several cell culture systems. This study was undertaken to determine whether propofol has neurotoxic effects on peripheral, retinal, and autonomic neurons, and which neurons are particularly liable to injury by propofol.
Method:
Dorsal root ganglia, retinal ganglion cell layers, and sympathetic ganglion chains were isolated from day eight chick embryos and cultured for 20 hr. Thereafter, propofol was added at various concentrations [5-300 microM (0.9-53 microg x mL(-1))] to investigate its effects on these three types of neuronal tissue. Morphological changes were examined quantitatively by growth cone collapse assay. Propofol concentrations were measured using high performance liquid chromatography.
Results:
Propofol induced growth cone collapse and neurite destruction. The three types of neurons tested exhibited significantly different dose-response relationships two hours after the application of propofol (P < 0.001) but not at 24 hr after application. The growth cone-collapsing effect was at least partially reversible in all three types of neurons after exposure to 100 microM propofol up to six hours, though reversibility was not observed after 24-hr exposure.
Conclusion:
While the clinical safety profile of propofol has been well documented, at high concentrations propofol has potential neurotoxicity on growing neurons in vitro.
Insights
High concentrations of propofol can cause neurotoxicity in developing neurons, leading to growth cone collapse and neurite destruction. This effect is dose-dependent and partially reversible in peripheral, retinal, and autonomic neurons.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Propofol is a widely used anesthetic agent.
- Previous studies suggest propofol may exhibit neurotoxic properties in vitro.
Purpose of the Study:
- To investigate the neurotoxic effects of propofol on peripheral, retinal, and autonomic neurons.
- To identify neuronal subtypes particularly susceptible to propofol-induced injury.
Main Methods:
- Isolation and culture of chick embryo dorsal root ganglia, retinal ganglion cells, and sympathetic ganglia.
- Exposure to varying concentrations of propofol (5-300 microM).
- Quantitative assessment of morphological changes using growth cone collapse assay.
Main Results:
- Propofol induced growth cone collapse and neurite destruction in all tested neuronal types.
- Significant dose-response relationships were observed within 2 hours, but not at 24 hours.
- Neurotoxic effects were partially reversible up to 6 hours post-exposure to 100 microM propofol.
Conclusions:
- Propofol exhibits potential neurotoxicity on developing neurons at high concentrations in vitro.
- Peripheral, retinal, and autonomic neurons show differential susceptibility to propofol-induced damage.
- Understanding these neurotoxic potentials is crucial despite propofol's established clinical safety.

