Abstract
3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), an effective free radical scavenger, provides neuroprotection in stroke models and patients. In this study, we investigated its neuroprotective effects in a chronic rotenone rat model for Parkinson's disease. Here we showed that a five-week treatment with edaravone abolished rotenone's activity to induce catalepsy, damage mitochondria and degenerate dopamine neurons in the midbrain of rotenone-treated rats. This abolishment was attributable at least partly to edaravone's inhibition of rotenone-induced reactive oxygen species production or apoptotic promoter Bax expression and its up-regulation of the vesicular monoamine transporter 2 (VMAT2) expression. Collectively, edaravone may provide novel clinical therapeutics for PD.
Highlights
Parkinson’s Disease (PD), characterized by tremor, rigidity, bradykinesia, and postural instability, is the second most common neurodegenerative disease which affects 1.7% of population aging sixty-five or elder [1,2]
We have shown that the main pharmacologic features of edaravone’s effective neuroprotection include: 1) attenuation of rotenone-induced characteristic parkinsonian behaviors in rats; 2) prevention of rotenone-induced over-generation of reactive oxygen species (ROS) in midbrain; 3) inhibition of apoptotic protein Bax expression in the SNc of rotenone-treated rats; 4) prevention of rotenoneinduced pathological changes in peripheral organs; 5) protection of mitochondria in SNc neurons against rotenone toxicity; and 6) upregulation of vesicular monoamine transporter 2 (VMAT2) expression
We have previously reported that both rotenone-based stereotaxical and systemic parkinsonian rodent models could recapitulate nigrostriatal DA lesions and mimic the clinical features of idiopathic PD
Summary
Parkinson’s Disease (PD), characterized by tremor, rigidity, bradykinesia, and postural instability, is the second most common neurodegenerative disease which affects 1.7% of population aging sixty-five or elder [1,2]. Neuroprotective effects of edaravone are shown in neonatal hypoxic-ischemic encephalopathy [7], acute intracerebral hemorrhage [6,8], subarachnoid hemorrhage [9], amyotrophic lateral sclerosis [10], traumatic brain injury [11,12] either animal models or patients In all of these diseases, free radicals contribute to neuronal death. In PD, protein aggregation further generates cellular stresses that can initiate or feed into pathways to cell death evoked by oxidative stress [13]. These results illumine that edaravone may protect dopaminergic (DA) neurons and slow down the neurodegeneration in PD through anti-oxidative mechanisms
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