Edaravone: A new therapeutic approach for the treatment of acute stroke Kiyoshi Kikuchi a, * , Ko-ichi Kawahara b,1 , Naohisa Miyagi a , Hisaaki Uchikado c , Terukazu Kuramoto d , Yoko Morimoto e , Salunya Tancharoen f , Naoki Miura g , Kazunori Takenouchi b , Yoko Oyama b , Binita Shrestha b , Fumiyo Matsuda h , Yoshihiro Yoshida h , Shinichiro Arimura i , Kentaro Mera j , Ko-ichi Tada j , Narimasa Yoshinaga b , Ryuichi Maenosono b , Yoshiko Ohno b , Teruto Hashiguchi b , Ikuro Maruyama b , Minoru Shigemori c a Department of Neurosurgery, Yame Public General Hospital, 540-2 Takatsuka, Yame 834-0034, Japan b Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan c Department of Neurosurgery, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan d Department of Neurosurgery, Omuta City General Hospital, 2-19-1 Takarazaka, Omuta, Fukuoka 836-8567, Japan e Department of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan f Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Rd., Rajthevee, Bangkok 10400, Thailand g Veterinary Teaching Hospital and Laboratory of Veterinary Diagnostic Imaging, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan h Division of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima 890-8506, Japan i Developmental Therapeutics Course, Oral and Maxillofacial Rehabilitation, Department of Maxillofacial Diagnostic and Surgical Science, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan j Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan article info Article history: Received 29 April 2010 Accepted 17 July 2010 summary Acute stroke, including acute ischemic stroke (AIS) and acute hemorrhagic stroke, (AHS) is a common medical problem with particular relevance to the demographic changes in industrialized societies. In recent years, treatments for AIS have emerged, including thrombolysis with tissue plasminogen activator (t-PA). Although t-PA is the most effective currently available therapy, it is limited by a narrow therapeu- tic time window and side effects, and only 3% of all AIS patients receive thrombolysis. Edaravone was originally developed as a potent free radical scavenger and, since 2001, has been widely used to treat AIS in Japan. It was shown that edaravone extended the narrow therapeutic time window of t-PA in rats. The therapeutic time window is very important for the treatment of AIS, and early edaravone treatment is more effective. Thus, more AIS patients might be rescued by administering edaravone with t-PA. Mean- while, edaravone attenuates AHS-induced brain edema, neurologic deficits and oxidative injury in rats. Although edaravone treatment is currently only indicated for AIS, it does offer neuroprotective effects against AHS in rats. Therefore, we hypothesize that early administration of edaravone can rescue AHS patients as well as AIS patients. Taken together, our findings suggest that edaravone should be immedi- ately administered on suspicion of acute stroke, including AIS and AHS. Ó 2010 Elsevier Ltd. All rights reserved. Background Stroke results in rapid loss of brain functions due to altered blood and oxygen supply to the brain, caused by a blocked or burst blood vessel. This can be due to acute ischemic stroke (AIS) caused by thrombosis or embolism, or due to acute hemorrhagic stroke (AHS) [1]. As a result, the affected area of the brain is unable to function, leading to an inability to move one or more limbs on one side of the body, an inability to understand or formulate speech, or an inability to see one side of the visual field [2]. A stroke is a medical emergency and can result in permanent neurological damage, complications, and death. Furthermore, it is the leading cause of adult disability in the United States and Europe, and is currently the second most common cause of death worldwide. Worryingly, stroke may become the leading cause of death worldwide [3]. Despite tremendous efforts in stroke research and significant improvements in stroke care within the last decade, there are still very few effective treatments for stroke [4]. To date, the only approved treatment for ischemic stroke is intravenous 0306-9877/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2010.07.038 * Corresponding author. Tel.: +81 943 23 4131; fax: +81 943 22 3185. E-mail address: kkikuchi@m2.kufm.kagoshima-u.ac.jp (K. Kikuchi). 1 This author contributed equally to this work. Medical Hypotheses 75 (2010) 583–585 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy