Small temperature variations alter edaravone-induced neuroprotection of cortical cultures exposed to prolonged hypoxic episodes.
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 degrees C), normothermia (37 degrees C), and mild hyperthermia (39 degrees 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 microM edaravone significantly improved the mean survival to 40.5 (4.7)%. This improvement was noted at higher doses of edaravone (5 microM < or =) but not at lower doses (< or =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.
Shibuta
S
S
Department of Anaesthesiology and Intensive Care Medicine, Graduate School of Medicine D7, Osaka University, 2-2, Yamadaoka, Suita 565-0871, Japan. shibuta@anes.med.osaka-u.ac.jp
Varathan
S
S
Kamibayashi
T
T
Mashimo
T
T
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine