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Brimonidine may have great potential to protect neurons against various stresses. Ma et al. recently clarified an additional neuroprotetive effect of brimonidine in the rat optic nerve crush model. In this study, brimonidine 1 mg/Kg was intraperitoneally injected before the optic nerve crush and daily thereafter. Four weeks after the crush, the survival in the brimonidine-treated group increased about 20% compared to that in vehicle-treated group. Prior experiments with brimonidine in animal models mimicking glaucoma or optic nerve damage have showed its beneficial effect. However, only a few papers have tried to clarify the mechanism of its effect. It has been suggested that the increase of neurotrophic factors or decrease of glutamate toxicity by brimonidine may be related to its mechanism. Although it is important to build up the neuroprotective results, it would be of even more interest to clarify the mechanism of neuroprotection induced by various drugs, including brimonidine. Unfortunately, not only in neuronal diseases, but also in glaucoma, many candidate drugs have not shown any definite evidence for neuroprotection in a clinical study.