Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction (Review)

Kikuchi,Kiyoshi; Kawahara,Ko-ichi; Uchikado,Hisaaki; Miyagi,Naohisa; Kuramoto,Terukazu; Miyagi,Tomoya; Morimoto,Yoko; Ito,Takashi; Tancharoen,Salunya; Miura,Naoki; Takenouchi,Kazunori; Oyama,Yoko; Shrestha,Binita; Matsuda,Fumiyo; Yoshida,Yoshihiro; Arimura,Shinihiro; Mera,Kentaro; Tada,Ko-ichi; Yoshinaga,Narimasa; Maenosono,Ryuichi; Ohno,Yoshiko; Hashiguchi,Teruto; Maruyama,Ikuro; Shigemori,Minoru

doi:10.3892/etm.2011.281

Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction (Review)

Authors:
- Kiyoshi Kikuchi
- Ko-ichi Kawahara
- Hisaaki Uchikado
- Naohisa Miyagi
- Terukazu Kuramoto
- Tomoya Miyagi
- Yoko Morimoto
- Takashi Ito
- Salunya Tancharoen
- Naoki Miura
- Kazunori Takenouchi
- Yoko Oyama
- Binita Shrestha
- Fumiyo Matsuda
- Yoshihiro Yoshida
- Shinihiro Arimura
- Kentaro Mera
- Ko-ichi Tada
- Narimasa Yoshinaga
- Ryuichi Maenosono
- Yoshiko Ohno
- Teruto Hashiguchi
- Ikuro Maruyama
- Minoru Shigemori
View Affiliations

Affiliations: Department of Neurosurgery, Yame Public General Hospital, Yame 834-0034, Japan, 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, Kagoshima 890-8520, Japan, Department of Neurosurgery, Kurume University School of Medicine, Kurume 830-0011, Japan, Department of Neurosurgery, Yame Public General Hospital, Yame 834-0034, Japan, Department of Neurosurgery, Omuta City General Hospital, Fukuoka 836‑8567, Japan, Department of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan, Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand, Veterinary Teaching Hospital and Laboratory of Veterinary Diagnostic Imaging, Faculty of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan, Division of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima 890-8506, Japan, Division of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima 890-8506, Japan, Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Neurosurgery, Kurume University School of Medicine, Kurume 830-0011, Japan
Published online on: June 7, 2011 https://doi.org/10.3892/etm.2011.281
Pages: 771-775

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Edaravone was originally developed as a potent free radical scavenger and has been widely used to treat cerebral infarction in Japan since 2001. Several free radical scavengers have been developed and some of them have progressed to clinical trials for the treatment of cerebral infarction. One such scavenger, edaravone, has been approved by the regulatory authority in Japan for the treatment of patients with cerebral infarction. Of particular interest is the ability of edaravone to diffuse into the central nervous system in various neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone has been found to have beneficial effects on inflammation, matrix metalloproteinases, nitric oxide production and apoptotic cell death. Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. The proven safety of edaravone following 9 years of use as a free radical scavenger suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.

View Figures

View References

1.	Adams HP Jr, del Zoppo G, Alberts MJ, et al: Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 38:1655–1711. 2007.
2.	Kikuchi K, Kawahara K, Tancharoen S, et al: The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells. J Pharmacol Exp Ther. 329:865–874. 2009. View Article : Google Scholar : PubMed/NCBI
3.	Kikuchi K, Tancharoen S, Matsuda F, et al: Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. Biochem Biophys Res Commun. 390:1121–1125. 2009. View Article : Google Scholar : PubMed/NCBI
4.	Higashi Y, Jitsuiki D, Chayama K and Yoshizumi M: Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger for treatment of cardiovascular diseases. Recent Pat Cardiovasc Drug Discov. 1:85–93. 2006. View Article : Google Scholar : PubMed/NCBI
5.	Lapchak PA and Zivin JA: The lipophilic multifunctional antioxidant edaravone (Radicut) improves behavior following embolic strokes in rabbits: a combination therapy study with tissue plasminogen activator. Exp Neurol. 215:95–100. 2009. View Article : Google Scholar
6.	Wang CX and Shuaib A: Neuroprotective effects of free radical scavengers in stroke. Drugs Aging. 24:537–546. 2007. View Article : Google Scholar : PubMed/NCBI
7.	Green AR and Shuaib A: Therapeutic strategies for the treatment of stroke. Drug Discov Today. 11:681–693. 2006. View Article : Google Scholar : PubMed/NCBI
8.	Van der Worp HB, Kappelle LJ, Algra A, et al: The effect of tirilazad mesylate on infarct volume of patients with acute ischemic stroke. Neurology. 58:133–135. 2002.PubMed/NCBI
9.	Shuaib A, Lees KR, Lyden P, et al: NXY-059 for the treatment of acute ischemic stroke. N Engl J Med. 357:562–571. 2007. View Article : Google Scholar : PubMed/NCBI
10.	Edaravone Acute Infarction Study Group: Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis. 15:222–229. 2003. View Article : Google Scholar
11.	Zhang N, Komine-Kobayashi M, Tanaka R, Liu M, Mizuno Y and Urabe T: Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke. 36:2220–2225. 2005. View Article : Google Scholar
12.	Unno Y, Katayama M and Shimizu H: Does functional outcome in acute ischaemic stroke patients correlate with the amount of free-radical scavenger treatment? A retrospective study of edaravone therapy. Clin Drug Investig. 30:143–155. 2010. View Article : Google Scholar
13.	Papadopoulos MC, Krishna S and Verkman AS: Aquaporin water channels and brain edema. Mt Sinai J Med. 69:242–248. 2002.PubMed/NCBI
14.	Yagi K, Kitazato KT, Uno M, et al: Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. Stroke. 40:626–631. 2009. View Article : Google Scholar : PubMed/NCBI
15.	Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N and Tada N: Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev. 12:9–20. 2006. View Article : Google Scholar : PubMed/NCBI
16.	Feigin VL and Findlay M: Advances in subarachnoid hemorrhage. Stroke. 37:305–308. 2006. View Article : Google Scholar : PubMed/NCBI
17.	Van Gijn J, Kerr RS and Rinkel GJ: Subarachnoid haemorrhage. Lancet. 369:306–318. 2007.
18.	Wiebers DO, Whisnant JP, Huston J III, et al: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 362:103–110. 2003. View Article : Google Scholar : PubMed/NCBI
19.	Aoki T, Nishimura M, Kataoka H, Ishibashi R, Nozaki K and Hashimoto N: Reactive oxygen species modulate growth of cerebral aneurysms: a study using the free radical scavenger edaravone and p47phox(−/−) mice. Lab Invest. 89:730–741. 2009.PubMed/NCBI
20.	Dorsch NW and King MT: A review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage Part I: incidence and effects. J Clin Neurosci. 1:19–26. 1994. View Article : Google Scholar : PubMed/NCBI
21.	Nakagomi T, Yamakawa K, Sasaki T, Saito I and Takakura K: Effect of edaravone on cerebral vasospasm following experimental subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 12:17–21. 2003. View Article : Google Scholar : PubMed/NCBI
22.	Munakata A, Ohkuma H, Nakano T, Shimamura N, Asano K and Naraoka M: Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 64:423–429. 2009. View Article : Google Scholar : PubMed/NCBI
23.	Tosaka M, Hashiba Y, Saito N, Imai H, Shimizu T and Sasaki T: Contractile responses to reactive oxygen species in the canine basilar artery in vitro: selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger. Acta Neurochir. 144:1305–1310. 2002. View Article : Google Scholar
24.	Nakamura T, Kuroda Y, Yamashita S, et al: Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke. 39:463–469. 2008. View Article : Google Scholar : PubMed/NCBI
25.	Fayad PB and Awad IA: Surgery for intracerebral hemorrhage. Neurology. 51:S69–S73. 1998. View Article : Google Scholar
26.	McDonald JW and Sadowsky C: Spinal-cord injury. Lancet. 359:417–425. 2002. View Article : Google Scholar
27.	Andersson U, Wang H, Palmblad K, et al: High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 192:565–570. 2000. View Article : Google Scholar : PubMed/NCBI
28.	Ao Q, Wang AJ, Chen GQ, Wang SJ, Zuo HC and Zhang XF: Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries. Med Hypotheses. 69:1234–1237. 2007. View Article : Google Scholar : PubMed/NCBI
29.	Rosenfeld JV, Bandopadhayay P, Goldschlager T and Brown DJ: The ethics of the treatment of spinal cord injury: stem cell transplants, motor neuroprosthetics, and social equity. Top Spinal Cord Inj Rehabil. 14:76–88. 2008. View Article : Google Scholar : PubMed/NCBI
30.	Aoyama T, Hida K, Kuroda S, et al: Edaravone (MCI-186) scavenges reactive oxygen species and ameliorates tissue damage in the murine spinal cord injury model. Neurol Med Chir. 48:539–545. 2008. View Article : Google Scholar : PubMed/NCBI
31.	Suzuki K, Kazui T, Terada H, et al: Experimental study on the protective effects of edaravone against ischemic spinal cord injury. J Thorac Cardiovasc Surg. 130:1586–1592. 2005. View Article : Google Scholar : PubMed/NCBI
32.	Takahashi G, Sakurai M, Abe K, Itoyama Y and Tabayashi K: MCI-186 prevents spinal cord damage and affects enzyme levels of nitric oxide synthase and Cu/Zn superoxide dismutase after transient ischemia in rabbits. J Thorac Cardiovasc Surg. 126:1461–1466. 2003. View Article : Google Scholar : PubMed/NCBI
33.	Takahashi G, Sakurai M, Abe K, Itoyama Y and Tabayashi K: MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia. Ann Thorac Surg. 78:602–607. 2004. View Article : Google Scholar : PubMed/NCBI
34.	Ohta S, Iwashita Y, Takada H, Kuno S and Nakamura T: Neuroprotection and enhanced recovery with edaravone after acute spinal cord injury in rats. Spine. 30:1154–1158. 2005. View Article : Google Scholar : PubMed/NCBI
35.	Maas AI, Stocchetti N and Bullock R: Moderate and severe traumatic brain injury in adults. Lancet Neurol. 7:728–741. 2008. View Article : Google Scholar : PubMed/NCBI
36.	Greenwald BD, Burnett DM and Miller MA: Congenital and acquired brain injury. 1 Brain injury: epidemiology and pathophysiology. Arch Phys Med Rehabil. 84:S3–S7. 2003. View Article : Google Scholar : PubMed/NCBI
37.	Chirumamilla S, Sun D, Bullock MR and Colello RJ: Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J Neurotrauma. 19:693–703. 2002. View Article : Google Scholar : PubMed/NCBI
38.	Rice AC, Khaldi A, Harvey HB, et al: Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp Neurol. 183:406–417. 2003. View Article : Google Scholar : PubMed/NCBI
39.	Itoh T, Satou T, Nishida S, et al: Edaravone protects against apoptotic neuronal cell death and improves cerebral function after traumatic brain injury in rats. Neurochem Res. 35:348–355. 2009. View Article : Google Scholar : PubMed/NCBI
40.	Itoh T, Satou T, Nishida S, Tsubaki M, Hashimoto S and Ito H: The novel free radical scavenger, edaravone, increases neural stem cell number around the area of damage following rat traumatic brain injury. Neurotox Res. 16:378–389. 2009. View Article : Google Scholar : PubMed/NCBI
41.	Dohi K, Satoh K, Mihara Y, et al: Alkoxyl radical-scavenging activity of edaravone in patients with traumatic brain injury. J Neurotrauma. 23:1591–1599. 2006. View Article : Google Scholar : PubMed/NCBI
42.	Dohi K, Satoh K, Nakamachi T, et al: Does edaravone (MCI-186) act as an antioxidant and a neuroprotector in experimental traumatic brain injury? Antioxid Redox Signal. 9:281–287. 2007. View Article : Google Scholar : PubMed/NCBI
43.	Raibon E, Todd LM and Moller T: Glial cells in ALS: the missing link? Phys Med Rehabil Clin N Am. 19:441–459. 2008. View Article : Google Scholar : PubMed/NCBI
44.	Mitchell JD and Borasio GD: Amyotrophic lateral sclerosis. Lancet. 369:2031–2041. 2007. View Article : Google Scholar : PubMed/NCBI
45.	Rosen DR, Siddique T, Patterson D, et al: Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 362:59–62. 1993. View Article : Google Scholar
46.	Ito H, Wate R, Zhang J, et al: Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice. Exp Neurol. 213:448–455. 2008. View Article : Google Scholar : PubMed/NCBI
47.	Kabashi E and Durham HD: Failure of protein quality control in amyotrophic lateral sclerosis. Biochim Biophys Acta. 1762:1038–1050. 2006. View Article : Google Scholar : PubMed/NCBI
48.	Valentine JS and Hart PJ: Misfolded CuZnSOD and amyotrophic lateral sclerosis. Proc Natl Acad Sci USA. 100:3617–3622. 2003. View Article : Google Scholar : PubMed/NCBI
49.	Yoshino H and Kimura A: Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study). Amyotroph Lateral Scler. 7:241–245. 2006. View Article : Google Scholar : PubMed/NCBI
50.	Takahashi R: Edaravone in ALS. Exp Neurol. 217:235–236. 2009. View Article : Google Scholar : PubMed/NCBI
51.	De Lau LM and Breteler MM: Epidemiology of Parkinson’s disease. Lancet Neurol. 5:525–535. 2006.
52.	Yuan WJ, Yasuhara T, Shingo T, et al: Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons. BMC Neurosci. 9:752008. View Article : Google Scholar : PubMed/NCBI
53.	Ma L, Cao TT, Kandpal G, et al: Genome-wide microarray analysis of the differential neuroprotective effects of antioxidants in neuroblastoma cells overexpressing the familial Parkinson’s disease alpha-synuclein A53T mutation. Neurochem Res. 35:130–142. 2010.PubMed/NCBI
54.	Rosati G: The prevalence of multiple sclerosis in the world: an update. Neurol Sci. 22:117–139. 2001. View Article : Google Scholar : PubMed/NCBI
55.	Cohen JA: Emerging therapies for relapsing multiple sclerosis. Arch Neurol. 66:821–828. 2009. View Article : Google Scholar
56.	Motomura K, Ogura M, Natsume A, Yokoyama H and Wakabayashi T: A free-radical scavenger protects the neural progenitor cells in the dentate subgranular zone of the hippocampus from cell death after X-irradiation. Neurosci Lett. 485:65–70. 2010. View Article : Google Scholar : PubMed/NCBI
57.	Anderson VA, Godber T, Smibert E, Weiskop S and Ekert H: Cognitive and academic outcome following cranial irradiation and chemotherapy in children: a longitudinal study. Br J Cancer. 82:255–262. 2000.PubMed/NCBI
58.	Crossen JR, Garwood D, Glatstein E and Neuwelt EA: Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol. 12:627–642. 1994.PubMed/NCBI
59.	Monje ML and Palmer T: Radiation injury and neurogenesis. Curr Opin Neurol. 16:129–134. 2003. View Article : Google Scholar : PubMed/NCBI
60.	Ishii J, Natsume A, Wakabayashi T, et al: The free-radical scavenger edaravone restores the differentiation of human neural precursor cells after radiation-induced oxidative stress. Neurosci Lett. 423:225–230. 2007. View Article : Google Scholar