Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice

摘要: In addition to its functions as a neuronal messenger molecule, nitric oxide (NO) has also been implicated in playing major role ischemic damage and glutamate neurotoxicity. Using primary cortical cultures from transgenic NO synthase (NOS) null (nNOS-) mice, we definitively establish mediator of NMDA hypoxic Neurotoxicity elicited by is markedly attenuated nNOS- compared with wild-type cultures. The NOS inhibitor nitro-L-arginine neuroprotective but not cultures, confirming the nNOS-derived Confirming that lack NMDA-stimulated nNOS activity, did stimulate formation cGMP elevates Both wild- type are sensitive toxicity induced donors, indicating pathways stimulated result cell death still intact mice. Superoxide dismutase against neurotoxicity both highlighting importance superoxide anion subsequent damage. unknown cellular factors endow differential resistance susceptibility quisqualate remain because response somatostatin-immunopositive neurons high-dose low-dose identical NOS-immunopositive There no difference kainate between only modest neurotoxicity, observations NO-mediated associated primarily activation receptor. protected 60 min combined oxygen-glucose deprivation Wild-type receptor antagonist MK-801 L- nitroarginine methyl ester, inactive stereoisomer D- ester. were additionally protected. These data confirm receptors production mediators after insult.