The Journal of neuroscience : the official journal of the Society for Neuroscience
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Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice.
In addition to its functions as a neuronal messenger molecule, nitric oxide (NO) has also been implicated in playing a major role in ischemic damage and glutamate neurotoxicity. Using primary cortical cultures from transgenic neuronal NO synthase (NOS) null (nNOS-) mice, we definitively establish NO as a mediator of NMDA and hypoxic neurotoxicity. Neurotoxicity elicited by NMDA is markedly attenuated in nNOS- cortical cultures compared with wild-type cultures. ⋯ The nNOS- cultures are markedly protected from 60 min of combined oxygen-glucose deprivation neurotoxicity compared with wild-type cultures. Wild-type cultures are protected from neuronal cell death by the NMDA receptor antagonist MK-801 and the NOS inhibitor L-nitroarginine methyl ester, but not its inactive stereoisomer D-nitroarginine methyl ester. nNOS- cultures were not additionally protected. These data confirm that activation of NMDA receptors and production of NO are primary mediators of neuronal damage after ischemic insult.