Cell experiment:

Cell viability is quantified by MTT assay and trypan blue staining. MTT (5 mg/mL, 20 μL) is added to each well and incubated for 4 h at 37℃ after the drug treatments. The medium is removed and the cell pellet is dissolved in DMSO. Then, the optical density (OD) values are measured at 570 nm using an ELISA reader.

Edaravone is a strong novel free radical scavenger, and inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator.

Edaravone performs both preventative and therapeutic effects against toxicity of glutamate. Pretreatment of edaravone reduces the toxicity of glutamate towards SGNs. Edaravone reduces apoptosis and necrosis caused by glutamate. Pretreatment of edaravone (500 μM) reverses these changes to approximately normal levels. The protective effect of edaravone on SGNs against glutamate-induced apoptosis is associated with PI3K/Akt pathway and Bcl-2 protein family[4].

Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Post-reperfusion brain edema and hemorrhagic events induced by thrombolytic therapy may be reduced by edaravone pretreatment[1]. Edaravone significantly decreases infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm3) being significantly lower than that in the control rats (264.0 mm3). Edaravone treatment also decreases the postischemic hemorrhage volumes (53.4 mm3 in edaravone-treated rats vs 176.4 mm3 in controls). In addition, the ratio of hemorrhage volume to infarct volume is lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%)[2]. In edaravone (20 mg/kg)-treated rats, astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) are decreased on the corpus callosum, germinal matrix, and cerebral cortex[3].

References:
[1]. Yoshida, H., et al. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev, 2006. 12(1): p. 9-20.
[2]. Okamura, K., et al. Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia. Neurol Res, 2013.
[3]. Garcia CA, et al. Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus. Childs Nerv Syst. 2016 Dec 17. [Epub ahead of print]
[4]. Bai X, et al. Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons. Neural Plast. 2016;2016:4034218. Epub 2016 Nov 10.