Adverse effects of methylene blue on the central nervous system
Laszlo Vutskits1, Adrian Briner, Paul Klauser
1Division of Anesthesiology, University Hospitals of Geneva, and Department of Neuroscience, Faculty of Medicine, Geneva University, Geneva, Switzerland. laszlo.vutskits@hcuge.ch
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.
Insights
Methylene blue (MB) can cause neurotoxicity, impacting central nervous system function and neuronal structure. This study investigated MB
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Clinical observations suggest adverse neurologic outcomes following methylene blue (MB) infusion during parathyroid surgery.
- The potential neurotoxic effects of MB warrant thorough investigation.
Purpose of the Study:
- To investigate the neurotoxic effects of methylene blue (MB) using in vivo and in vitro experimental models.
- To evaluate the impact of MB on neuronal function, cell death, and dendritic structure.
Main Methods:
- In vivo studies in rats assessed hemodynamic responses and isoflurane MAC after MB administration, with neuronal apoptosis evaluated via Fluoro-Jade B and caspase-3 staining.
- In vitro studies utilized hippocampal slice cultures to measure excitatory field potentials and cell death, and neuronal cultures to assess dendritic arbor changes.
Main Results:
- MB administration significantly reduced isoflurane MAC and induced widespread neuronal apoptosis in vivo.
- In vitro, MB rapidly suppressed excitatory field potentials and caused dose-dependent cell death in hippocampal slices.
- MB exposure, even at non-lethal concentrations, led to significant dendritic arbor retraction in neuronal cultures.
Conclusions:
- Methylene blue exerts neurotoxic effects on the central nervous system.
- The findings raise concerns about the safety of high-dose MB use in parathyroid surgery.
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