Parkinson's disease (PD) is a neurodegenerative disorder characterized by slowly progressive degeneration of DA neurons in the substantia nigra pars compacta, with subsequent damage of nerve terminals accompanied by dopamine (DA) depletion in the striatum . Although the neuropathological hallmarks of PD are well described, the etiology remains still undefined. However, accumulative evidences revealed many biochemical processes and molecular mechanisms as mediators of neuronal cell death in PD. Notably oxidative stress and mitochondrial dysfunction might be an important pillar of pathogenesis of PD .
6-hydroxydopamine (6-OHDA) is widely used for experimental models of PD . It damages cells with dopaminergic neuronal attribute, including human neuroblastoma SH-SY5Y , PC12 cells derived from rat pheochromocytoma  and rat ventral mesencephalic neurons . Furthermore, it is also a specific neurotoxin for DA neurons in vivo [2, 7]. Intracellular lipids, proteins or DNA are damaged with consequent impairment of cell function induced by 6-OHDA. Mitochondrial oxidative phosphorylation with subsequent energy deprivation and excrement of 6-OHDA-auto-oxidation, including quinones and hydrogen peroxide (H2O2) are deeply involved in the cytotoxic processes . As above described, mitochondrial dysfunction and oxidative stress might play important roles in the pathogenesis of PD , thus indicating that the experimental model using 6-OHDA might have essential mechanisms in common with PD. Furthermore, anti-oxidant agents, such as catalase, vitamin E, N-acetyl cysteine, ascorbic acid and pyruvate might exert neuroprotection for 6-OHDA-treated DA neurons .
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger of hydroxyl radicals, and is useful for patients suffering from ischemic stroke [10, 11], with the involvement of peroxidation leading to neuronal cell death . Neuroprotective effects of edaravone are explored using head trauma  and spinal cord ischemia . Recent study demonstrated that edaravone suppress the production of nitric oxide and reactive oxygen species by activated microglia . In both cerebral ischemia and PD, free radicals might be one of the critical pathogenesis which accelerates progression of disease. These results suggest that edaravone might have neuroprotective effects on 6-OHDA-treated DA neurons and might on slowly degenerated DA neurons in PD patients through anti-oxidative mechanisms.
In this study, first we explored the neuroprotective effects of edaravone on 6-OHDA-induced toxicity against murine ventral mesencephalic (VM) cell cultures and the underlying mechanisms. After confirming the effects in vitro, edaravone was intravenously administered to 6-OHDA-lesioned PD model of rats and evaluated behaviorally and immunohistochemically.