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Propofol induces growth cone collapse and neurite retractions in chick explant culture

[Le propofol provoque un collapsus des cônes de croissance et des rétractions des neurites de poussin embryonnaire en culture]

Wael S. Al-Jahdari, MD^*, Shigeru Saito, MD PhD^*, Takashi Nakano, MD PhD and Fumio Goto, MD PhD^*

^* From the Departments of Anesthesiology, and
Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi-city, Gunma, Japan.

Address correspondence to: Dr. Shigeru Saito, Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-city, Gunma, 371-8511, Japan. Phone: +81-27220-8454; Fax: +81-27220-8473; E-mail: shigerus{at}showa.gunma-u.ac.jp

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 µM (0.9–53 µg·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 µM 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.

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