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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]

  • General Anesthesia
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Canadian Journal of Anesthesia/Journal canadien d'anesthésie Aims and scope Submit manuscript

Abstract

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.

Objectif

La neurotoxicité du propofol a été démontrée dans plusieurs systèmes de culture cellulaire. Notre étude cherche à déterminer si le propofol a des effets neurotoxiques sur les neurones périphériques, rétiniens et du système autonome, et quels neurones sont particulièrement susceptibles de subir des lésions causées par le propofol.

Méthode

Des ganglions de la racine dorsale, des couches cellulaires de la rétine et des chaînes sympathiques provenant d’embryons de poussin de huit jours ont été isolés et mis en culture pendant 20 h. Par la suite, différentes concentrations de propofol ont été ajoutées [5-300 μM (0,9-53 μg·mL-1)] pour étudier ses effets sur les trois types de tissu neuronal. Les changements morphologiques ont été évalués quantitativement par l’analyse du collapsus des cônes de croissance. La chromatographie liquide à haute performance a été utilisée pour mesurer les concentrations de propofol.

Résultats

Le propofol a provoqué un collapsus des cônes de croissance et la destruction des neurites. Les trois types de neurones testés ont affiché des relations dose-réponse significativement différentes, deux heures après l’application du propofol (P < 0,001) mais non à 24 h après l’application. L’effet de collapsus des cônes de croissance était au moins partiellement réversible dans les trois types de neurones après l’exposition à 100 μM de propofol pendant six heures ou moins, mais la réversibilité n’était plus observée après 24 h d’exposition.

Conclusion

Le profil de sécurité clinique du propofol est bien connu, mais à concentrations élevées, le propofol possède une neurotoxicité potentielle sur les neurones en développement in vitro.

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Authors and Affiliations

  1. Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, 371-8511, Maebashi-city, Gunma, Japan

    Wael S. Al-Jahdari, Shigeru Saito & Fumio Goto

  2. Departments of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi-city, Gunma, Japan

    Takashi Nakano

Authors
  1. Wael S. Al-Jahdari
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  2. Shigeru Saito
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  3. Fumio Goto
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  4. Takashi Nakano
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Corresponding author

Correspondence to Shigeru Saito.

Additional information

Financial support: This work was supported by research grants from the Japanese government to Saito S. and Goto F. (Ministry of Science, Education and Sports).

This work was supported by research grants from the Japanese government to Saito S. and Goto F. (Ministry of Science, Education and Sports).

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Al-Jahdari, W.S., Saito, S., Goto, F. et al. 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]. Can J Anesth 53, 1078–1085 (2006). https://doi.org/10.1007/BF03022874

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  • DOI: https://doi.org/10.1007/BF03022874

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