Adverse effects of methylene blue on the central nervous system

Laszlo Vutskits, Adrian Briner, Paul Klauser, Eduardo Gascon, Alexandre G. Dayer, J. Kiss, Dominique Muller, Marc J. Licker, Denis R. Morel

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: An increasing number of clinical observations suggest adverse neurologic outcome after methylene blue (MB) infusion in the setting of parathyroid surgery. Hence, the aim of the current study was to investigate the potentially neurotoxic effects of MB using a combination of in vivo and in vitro experimental approaches. METHODS: Isoflurane-anesthetized adult rats were used to evaluate the impact of a single bolus intravascular administration of MB on systemic hemodynamic responses and on the minimum alveolar concentration (MAC) of isoflurane using the tail clamp test. In vivo, MB-induced cell death was evaluated 24 h after MB administration using Fluoro-Jade B staining and activated caspase-3 immunohistochemistry. In vitro, neurotoxic effects of MB were examined in hippocampal slice cultures by measuring excitatory field potentials as well as propidium iodide incorporation after MB exposure. The impact of MB on dendritic arbor was evaluated in differentiated single cell neuronal cultures. RESULTS: Bolus injections of MB significantly reduced isoflurane MAC and initiated widespread neuronal apoptosis. Electrophysiologic recordings in hippocampal slices revealed a rapid suppression of evoked excitatory field potentials by MB, and this was associated with a dose-dependent effect of this drug on cell death. Dose-response experiments in single cell neuronal cultures revealed that a 2-h-long exposure to MB at non-cell-death-inducing concentrations could still induce significant retraction of dendritic arbor. CONCLUSIONS: These results suggest that MB exerts neurotoxic effects on the central nervous system and raise questions regarding the safety of using this drug at high doses during parathyroid gland surgery.

Original languageEnglish
Pages (from-to)684-692
Number of pages9
JournalAnesthesiology
Volume108
Issue number4
DOIs
Publication statusPublished - Apr 2008

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Methylene Blue
Central Nervous System
Isoflurane
Cell Death
Cell Culture Techniques
Parathyroid Glands
Propidium
Caspase 3
Pharmaceutical Preparations
Nervous System
Tail
Hemodynamics
Immunohistochemistry
Apoptosis
Staining and Labeling

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Vutskits, L., Briner, A., Klauser, P., Gascon, E., Dayer, A. G., Kiss, J., ... Morel, D. R. (2008). Adverse effects of methylene blue on the central nervous system. Anesthesiology, 108(4), 684-692. https://doi.org/10.1097/ALN.0b013e3181684be4

Adverse effects of methylene blue on the central nervous system. / Vutskits, Laszlo; Briner, Adrian; Klauser, Paul; Gascon, Eduardo; Dayer, Alexandre G.; Kiss, J.; Muller, Dominique; Licker, Marc J.; Morel, Denis R.

In: Anesthesiology, Vol. 108, No. 4, 04.2008, p. 684-692.

Research output: Contribution to journalArticle

Vutskits, L, Briner, A, Klauser, P, Gascon, E, Dayer, AG, Kiss, J, Muller, D, Licker, MJ & Morel, DR 2008, 'Adverse effects of methylene blue on the central nervous system', Anesthesiology, vol. 108, no. 4, pp. 684-692. https://doi.org/10.1097/ALN.0b013e3181684be4
Vutskits L, Briner A, Klauser P, Gascon E, Dayer AG, Kiss J et al. Adverse effects of methylene blue on the central nervous system. Anesthesiology. 2008 Apr;108(4):684-692. https://doi.org/10.1097/ALN.0b013e3181684be4
Vutskits, Laszlo ; Briner, Adrian ; Klauser, Paul ; Gascon, Eduardo ; Dayer, Alexandre G. ; Kiss, J. ; Muller, Dominique ; Licker, Marc J. ; Morel, Denis R. / Adverse effects of methylene blue on the central nervous system. In: Anesthesiology. 2008 ; Vol. 108, No. 4. pp. 684-692.
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