The significance of nitric oxide production in the brain after injury

Glutamate toxicity has been implicated in many aspects of brain injury including traumatic, ischemic, and hemorrhagic damage. We have used in vitro as well as in vivo methods to measure NO production and to examine the role of NO in glutamate toxicity. In building our recombinant system, we used human kidney embryonic cells, HEK 293, as host for transfection of nNOS and NMDA receptor proteins. Cells cotransfected with NMDA and nNOS were more resistant to glutamate toxicity. This resistance correlated with NO production as measured by citrulline assay. Meanwhile, the production of NO did not significantly change the response of the NMDA receptor as seen by calcium studies. Moreover, in vivo, NO production was directly correlated with brain tissue oxygen tension in subarachnoid hemorrhage patients. These data and others point toward the importance of NO production in the response of brain to injury.