BDNF OR IGF-I POTENTIATES FREE RADICAL-MEDIATED INJURY IN CORTICAL CELL-CULTURES

FREE radical-mediated damage to cultured cortical neurons was induced by a 24 h exposure to Fe2+ (30 mu M) or an inhibitor of gamma-glutamyl cysteine synthetase, L-buthionine-[S,R]-sulfoximine (BSO, 1 mM). As ex pected, neuronal death was blocked by inclusion of the free radical sc avenger trolox during the Fe2+ or BSO exposure. However, unexpectedly, pretreatment of the cultures with BDNF or IGF-I markedly potentiated neuronal death. This growth factor-potentiated death was still blocked by trolox, but was insensitive to glutamate antagonists. Concurrent a ddition of cycloheximide with the growth factors prevented injury pote ntiation. Present findings suggest that growth factors may increase fr ee radical-induced neuronal death by mechanisms dependent upon protein synthesis.