Edaravone Protects Neurons in the Rat Substantia Nigra Against 6-Hydroxydopamine-Induced Oxidative Stress Damage

Abstract

To investigate the mechanism of the neuroprotective effect of edaravone in substantia nigra (SN) of the 6-OHDA-induced rat model of Parkinson's disease. Animal model of Parkinson's disease was induced in male Sprague-Dawley rats by injecting 6-OHDA into the left medial forebrain bundle. Subsequently, rats were intraperitoneally injected with 0.3, 1, or 3 mg/kg of edaravone for 14 days or with 3 mg/kg edaravone for 14 days followed by 14 days of no treatment. We evaluated the effect of edaravone on the rotational and normal behavior of the rats, and on the number of tyrosine hydroxylase (TH)-positive cells, the amount of Nissl bodies, and the levels of glutathione (GSH), and malondialdehyde (MDA) in the SN. Edaravone treatment at 3 mg/kg significantly reduced apomorphine-induced rotational behavior (P < 0.01), improved the spontaneous behavior, prevented the decrease in the levels of TH-positive cells, Nissl bodies and GSH, and inhibited the increase in the levels of MDA (P < 0.05) in SN of rats with 6-OHDA-induced PD. Edaravone exerted a long-term neuroprotective effects in 6-OHDA-induced PD animal model by attenuating changes in the levels of GSH and MDA in SN, caused by oxidative stress. Edaravone prevented 6-OHDA-induced behavioral changes and de-pigmentation of SN that results from the loss of dopaminergic neurons.

Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress

“…It is known that L-Dopa can also damage dopaminergic (DA) neurons (Blessing et al, 2003; Mena et al, 2009) as chronic treatment is associated with the development of complications such as dyskinesia, motor fluctuation, and dementia (Liu et al, 2014). …”

Analysis of neuronal Ca2+handling properties by combining perforated patch clamp recordings and the added buffer approach

“…Given the stable and reliable recording conditions provided by β-escin, we combined β-escin perforated patch clamp recordings with ratiometric fura-2 Ca 2+ imaging to analyze Ca 2+ handling properties. Using the added buffer approach, we determined the resting Ca 2+ concentration ([Ca 2+ ] i ), the Ca 2+ binding ratio κ S, and the extrusion rate γ of SN DA neurons, which display Ca 2+ dependent endogenous pacemaking properties (Liu et al, 2014; Neuhoff et al, 2002; Smits et al, 2013). Neurons were held at −70 mV to avoid spontaneous spiking.…”

Protection by Edaravone, a Radical Scavenger, against Manganese‐Induced Neurotoxicity in Rats

“…Until now numerous studies have indicated the antioxidant, antiapoptotic, and anti‐inflammatory properties of EDA against toxic agents such as paraquat , 6‐hydroxydopamine , and rotenone . It has been reported that EDA could successfully preserve whole nigrostriatal dopaminergic systems against a 6‐hydroxydopamine‐induced rat model []. Another study demonstrated that a 5‐week treatment with EDA eliminated the toxic effects of rotenone on dopaminergic neurons by preventing ROS generation and mitochondrial damage .…”