Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons
Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of nigrostriatal dopaminergic systems. Free radicals induced by oxidative stress are involved in the mechanisms of cell death in PD.
This study clarifies the neuroprotective effects of Edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one), which has already been used for the treatment of cerebral ischemia in Japan, on dopaminergic neurons using PD model both in vitro and in vivo. 6-hydroxydopamine (6-OHDA), a neurotoxin for dopaminergic neurons, was added to cultured dopaminergic neurons derived from murine embryonal ventral mesencephalon with subsequet administration of edaravone or saline.
The number of surviving dopaminergic neurons and the degree of cell damage induced by free radicals were analyzed. In parallel, edaravone or saline was intravenously administered for PD model of rats receiving intrastriatal 6-OHDA lesion with subsequent behavioral and histological analyses.
Results: In vitro study showed that edaravone significantly ameliorated the survival of dopaminergic neurons in a dose-responsive manner.
The number of apoptotic cells and HEt-positive cells significantly decreased, thus indicating that the neuroprotective effects of edaravone might be mediated by anti-apoptotic effects through the suppression of free radicals by edaravone. In vivo study demonstrated that edaravone-administration at 30 minutes after 6-OHDA lesion reduced the number of amphetamine-induced rotations significantly in a dose-responsive manner than edaravone-administration at 24 hours.
Tyrosine hydroxylase (TH) staining of the striatum and substantia nigra pars compacta revealed that edaravone might exert neuroprotective effects on nigrostriatal dopaminergic systems. The neuroprotective effects were prominent when edaravone was administered early and in high concentration.
Furthermore, Iba-1 staining revealed that the inflammation was suppressed in rats receiving edaravone-administration.
Conclusions: Edaravone exerts neuroprotective effects on PD model both in vitro and in vivo through the anti-apoptotic effects via the suppression of free radicals with subsequent anti-inflammatory effects. Edaravone might be a safe and hopeful therapeutic option for PD.
Author: Wen Ji Yuan, Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Masahiro Kameda, Takashi Agari, Takashi Uozumi, Naoki Tajiri, Takamasa Morimoto, Feifei Wang, Meng Jing, Tanefumi Baba, Hanbai Liang, Toshihiro Matsui, Yasuyuki Miyoshi and Isao Date<
Published on: 2008-08-01
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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