Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons

Abstract

Background: 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 TH-positive 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 TH-positive 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.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

“…It has been used clinically to reduce neuronal damage resulting from cerebral ischemic stroke in Japan and China (Nakamura et al 2008). In addition, edaravone has displayed its protective effects in a variety of brain diseases, including traumatic brain injury (Ohta et al 2013), Alzheimer's disease (Yan et al 2012), and Parkinson's disease (Yuan et al 2008). Previous research has shown that edaravone plays an important role as a direct and indirect free radical scavenger by neutralizing toxic ROS and reactive nitrogen species (RNS) (Roh et al 2011).…”

The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson’s disease

“…The areas were then calculated and used for statistical analyses. Accordingly to our previous publications (Yuan et al, 2008;Kikuchi et al, 2011), for counting the number of TH-positive neurons, every fifth 40μm-thick coronal tissue section through the substantia nigra pars compacta (SNc) was explored using 3 coronal sections respectively at 4.8 and 5.3 mm posterior to the bregma.…”

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

“…Studies regarding its incidence report that it is between 8 and 18 per 100,000 individuals per year (51). Edaravone was found to exert neuroprotective effects on PD models both in vivo (52) and in vitro (52,53). The underlying mechanisms may involve anti-apoptotic, anti-oxidative and/or the anti-inflammatory effects of edaravone (52,53).…”

“…Edaravone was found to exert neuroprotective effects on PD models both in vivo (52) and in vitro (52,53). The underlying mechanisms may involve anti-apoptotic, anti-oxidative and/or the anti-inflammatory effects of edaravone (52,53). Edaravone may be a potential therapeutic agent for PD, although the high therapeutic dosage required is a problem for clinical applications (52,53).…”