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BJA Advance Access published online on November 18, 2009
British Journal of Anaesthesia, doi:10.1093/bja/aep320
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© The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org.

Small temperature variations alter edaravone-induced neuroprotection of cortical cultures exposed to prolonged hypoxic episodes

S. Shibuta*, S. Varathan, T. Kamibayashi and T. Mashimo

Department of Anaesthesiology and Intensive Care Medicine, Graduate School of Medicine D7, Osaka University, 2-2, Yamadaoka, Suita 565-0871, Japan

* Corresponding author. E-mail: shibuta{at}anes.med.osaka-u.ac.jp

Background: Edaravone, a free radical scavenger, has been shown to be neuroprotective in vivo and in vitro. However, the impact of small temperature variations on its neuroprotective actions remains unknown.

Methods: We examined the degree of neuroprotection conferred by various concentrations of edaravone on cortical cultures exposed to prolonged hypoxia (24 h) under three conditions: mild hypothermia (32°C), normothermia (37°C), and mild hyperthermia (39°C). The survival of cortical neurones from E16 Wistar rats (SR) was evaluated using photomicrographs taken before and after exposure to hypoxia.

Results: The mean survival of neurones exposed to hypoxia at normothermia was 14.7 (SEM 1.8)%. The addition of 50 µM edaravone significantly improved the mean survival to 40.5 (4.7)%. This improvement was noted at higher doses of edaravone (5 µM ≤) but not at lower doses (≤500 nM). With mild hypothermia and prolonged hypoxia without edaravone, neuroprotection was significantly improved with a mean survival of 63.0 (5.2)%. This neuroprotective effect was not enhanced with the addition of edaravone, even at the highest dose. Hypoxia-induced neurotoxicity was aggravated by mild hyperthermia as reflected by a mean survival of 9.1 (2.1)%. However, higher concentrations of edaravone inhibited the deleterious effect of mild hyperthermia, thereby demonstrating a significant neuroprotective effect. The survival of neurones subjected to both hyperthermia and edaravone was the same as that of neurones exposed to normothermia and edaravone.

Conclusions: Temperature is a potential factor in determining whether edaravone confers a neuroprotective effect when applied during prolonged hypoxic insults.

Keywords: complications, hypoxia; complications, hyperthermia; hypothermia; model, rat, fetal; temperature, body


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