Antagonistic effect of nerve growth factor on neuronal injury induced by hypoxia in cultured cerebral cortical neurons of rats

AIM: To observe the effects of nerve growth factor (NGF) on neuronal hypoxic injury induced by sodium dithionite in primary cultures from gestation of 17-d rat fetal cerebral cortex. METHODS: Neuronal death and lactate dehydrogenase (LDH) efflux in the bathing medium were measured. The homogenate of cortical cells was used to determine malonyldialdehyde (MDA) content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. RESULTS: When cultures were incubated for 24 h with sodium dithionite, efflux of LDH and MDA content increased while the number of surviving neurons decreased. NGF 100 mu g.L-1 increased the number of surviving neurons to 85 % +/- 9 % of normoxia level under hypoxia. NGF 1 - 100 mu g.L-1 concentration-dependently attenuated hypoxia-induced increase of efflux of LDH and MDA content, with IC50 Of 27 and 49 (95 % confidence limits: 18 - 49 and 29 - 110) mu g.L-1. NGF 30 mu g.L-1 induced a 3-fold increase in SOD and GSH-Px activities. The levels of SOD and GSH-Px activities in hypoxia group were increased 2.7-fold by NGF 100 mu g.L-1. CONCLUSION: NGF prevented hypoxic insults in cultured cerebral cortical neurons by suppressing the generation of lipid peroxides and increasing the activities of antioxidant enzymes.