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Effects of propofol on N-methyl-d-aspartate receptor-mediated calcium increase in cultured rat cerebrocortical neurons

Published online by Cambridge University Press:  02 June 2005

C. Grasshoff
Affiliation:
Eberhard-Karls-University, Department of Anaesthesiology and Intensive Care, Tuebingen, Germany GAF Pharmacological Institute, Muenchen, Germany
T. Gillessen
Affiliation:
GAF Pharmacological Institute, Muenchen, Germany Present address: Dachau General Hospital, Department of Neurology, Krankenhausstrasse 15, 85221 Dachau, Germany.
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Summary

Background and objective: The intravenous anaesthetic propofol has been reported to exert neuroprotective actions by several mechanisms. This study has been designed to investigate the effects of propofol on intracellular calcium increase in cultured cerebrocortical neurons after exposure to pathological concentrations of N-methyl-d-aspartate (NMDA) mediated by potential direct interactions of propofol with NMDA receptors.

Methods: The effects of propofol (0.1–100 μmol) on intracellular calcium increase induced by 300 μmol NMDA (180 s) were measured in cultured cerebrocortical neurons using the calcium-sensitive fluorochrome calcium green-5N-acetoxymethylester with confocal laser scanning microscopy.

Results: The intraneuronal calcium increase after exposure to 300 μmol NMDA depended on extracellular calcium concentration. Propofol reduced the increase of NMDA receptor-induced intraneuronal calcium concentration dependently with a threshold concentration for a significant effect of 10 μmol. The overall effect was small, since even high concentrations of propofol (100 μmol) diminished intraneuronal calcium rise by only 50%.

Conclusions: The threshold concentration for significant effects of propofol on the NMDA-induced increase of intraneuronal calcium turned out to be in the upper limit of propofol concentrations that are considered to be clinically relevant. However, in the presence of high propofol concentrations, inhibition of NMDA receptor-mediated calcium increase might contribute to neuroprotective effects observed with propofol.

Type
Original Article
Copyright
© 2005 European Society of Anaesthesiology

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