Edaravone Guards Dopamine Neurons Figure 8. Working model for protective effect of edaravone on DA neurons. Up-regulation of VMAT2 expression by edaravone treatments to reduce cytosolic dopamine concentration, along with down-regulation of apoptosis pathways, may make DA neurons healthier. doi:10.1371/journal.pone.0020677.g008 Figure S1 (TIF) Figure S2 (TIF) References edaravone is an excellent method to prevent DA neurons from degeneration in rotenone-induced parkinsonian model, it is expected that treatment of edaravone may slow down the progression of neurodegeneration in patients with PD, as observed in those with stroke. Supporting Information Primers for qRT-PCR. The chemical structure of edaravone. Figure S3 Effect of edaravone on Rotenone-induced body weight loss in rats. Statistical analysis showed significant difference in body weight between Rot-group animals and Veh- Figure S4 used. (TIF) group animals at all time points except on day 0 (P,0.05). No significant difference was found between Eda-group animals and Veh-group animals in the whole period of 5 weeks. (TIF) Experimental timeline with number of rats Author Contributions Conceived and designed the experiments: NX JX GK SS ZL TW YZ. Performed the experiments: NX JX GK CC JH YZ ZZ XQ YF HR. Analyzed the data: NX JX GK ZL TW. Contributed reagents/materials/ analysis tools: NX JX GK JH ZL YZ. Wrote the paper: NX JX GK ZL TW. 1. Zhang ZX, Roman GC, Hong Z, Wu CB, Qu QM, et al. (2005) Parkinson’s disease in China: prevalence in Beijing, Xian, and Shanghai. Lancet 365: 595–597. 2. Olanow CW, Stern MB, Sethi K (2009) The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology 72: S1–136. 3. Fukui H, Moraes CT (2008) The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? Trends Neurosci 31: 251–256. 4. Nunomura A, Moreira PI, Lee HG, Zhu X, Castellani RJ, et al. (2007) Neuronal death and survival under oxidative stress in Alzheimer and Parkinson diseases. CNS Neurol Disord Drug Targets 6: 411–423. 5. Sun F, Kanthasamy A, Anantharam V, Kanthasamy AG (2007) Environmental neurotoxic chemicals-induced ubiquitin proteasome system dysfunction in the pathogenesis and progression of Parkinson’s disease. Pharmacol Ther 114: 327–344. 6. Nakamura T, Kuroda Y, Yamashita S, Zhang X, Miyamoto O, et al. (2008) Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke 39: 463–469. 7. Noor JI, Ikeda T, Mishima K, Aoo N, Ohta S, et al. (2005) Short-term administration of a new free radical scavenger, edaravone, is more effective than its long-term administration for the treatment of neonatal hypoxic-ischemic encephalopathy. Stroke 36: 2468–2474. 8. Yagi K, Kitazato KT, Uno M, Tada Y, Kinouchi T, et al. (2009) Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. Stroke 40: 626–631. 9. Munakata A, Ohkuma H, Nakano T, Shimamura N, Asano K, et al. (2009) Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 64: 423-428; discussion 428-429. PLoS ONE | www.plosone.org 10 June 2011 | Volume 6 | Issue 6 | e20677