Ebselen prevents excitotoxicity provoked by glutamate in rat cerebellar granule neurons

Ebselen is a selenium compound that have glutathione peroxidase-like activi ty which is neuroprotective in acute stroke ischemia. The efficacy of ebsel en to prevent excitotoxicity provoked by glutamate in cerebellar granule ne urons was investigated at various time points and concentrations. Simultane ous addition of ebselen with glutamate decreased neuronal death and was com pletely reversed by 3 muM of ebselen (3 (4,5-dimethylthiazol-2-yl)-2,5-diph enyl tetrazolium bromide (MTT) and propidium iodide assays). However, when 1 muM of ebselen was added with glutamate and remained in the culture mediu m until 24 or 48 h, the neuronal survival increased to the control. The mec hanism proposed for neuroprotection was the ability of ebselen to prevent l ipoperoxidation provoked by glutamate. The present findings propose to ampl ify the use of ebselen in others neurodegenerative disorders involving glut amatergic system. (C) 2001 Elsevier Science Ireland Ltd. All rights reserve d.