• Kiyoshi Kikuchi, Ko-ichi Kawahara, Salunya Tancharoen, Fumiyo Matsuda, Yoko Morimoto, Takashi Ito, Kamal Krishna Biswas, Kazunori Takenouchi, Naoki Miura, Yoko Oyama, Yuko Nawa, Noboru Arimura, Masahiro Iwata, Yutaka Tajima, Terukazu Kuramoto, Kenji Nakayama, Minoru Shigemori, Yoshihiro Yoshida, Teruto Hashiguchi, and Ikuro Maruyama.
• Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Science, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
• J. Pharmacol. Exp. Ther. 2009 Jun 1;329(3):865-74.

AbstractEdaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 +/- 10.4 and 43.8 +/- 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 microM) suppressed OGD- and H(2)O(2)-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 microM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.

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