Effects of nerve growth factor on nitric oxide-mediated neurotoxicity in primary cortical cultures

Objective To observe the effects of nerve growth factor (NGF) on nitric oxi de (NO) release and constitutive nitric oxide synthase (cNOS) gene expressi on in oxygen/glucose deprived cortical neuron cultures. Methods Neuron viability was measured to assay NGF effect. The content of N O and the expression of cNOS mRNA were determined by spectrofluorometric me thod and Northern blot respectively. Results There were a marked increase of neuronal death and NO release in ox ygen/glucose deprived cultures for 24 h. NOS inhibitor, NG-nitro-L-arginine methyl ester (NAME) 100 mu mol . L-1 and NGF 50, 100 mu g . L-1, significa ntly increased neuronal surviving and decreased NO release. However, NGF (5 0, 100 mu g . L-1) had no significant effects on neurotoxicity induced by s odium nitroprusside (SNP) 300 mu mol . L-1 in cortical cultures. Hemoglobin (Hb), which binds NO, completely prevented hypoxia/hypoglycemia- or SNP-in duced cell death and NO release at 500 mu mol . L-1 NGF 100 mu g . L-1 sign ificantly attenuated cNOS gene expression. Conclusion NO can mediate the neurotoxicity of hypoxia/hypoglycemia, and NG F can protect cortical neurons against oxygen/glucose deprivation-induced t oxicity via inhibiting the activity of cNOS and suppressing the release of NO.