Edaravone alleviates hypoxia-acidosis/reoxygenation-induced neuronal injury by activating ERK1/2.

Edaravone, a free radical scavenger, is the first clinical drug of neuroprotection for ischemic stroke patients in the world, and has been shown to be an effective agent to alleviate cerebral ischemic injury. It has been established that acidosis is a common feature of cerebral ischemia and underlies the pathogenesis of ischemic stroke. In the present study, we investigated the role of edaravone in hypoxia-acidosis/reoxygenation (H-A/R)-induced neuronal injury that is partially mediated by the activation of acid-sensing ion channels (ASICs). Here, we observed that pretreatment of cultured neurons with edaravone largely reduced LDH release induced by acidosis or H-A/R. We also found that edaravone exhibited its neuroprotective roles by enhancing brain-derived neurotrophic factor (BDNF) and Bcl-2 expression, suppressing caspase-3 activity and promoting extracellular signal-regulated kinase1/2 (ERK1/2) activation. Furthermore, the addition of MEK (mitogen-activated protein kinase/ERK kinase) antagonists PD98059 and U0126 nearly abolished the beneficial effects of edaravone. Similarly, ASICs blockade produced the protective effects comparable to edaravone administration. These results indicate that edaravone is capable of attenuating H-A/R-mediated neurotoxicity at least partially through activating ERK1/2.