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Fig. 7. NO plays multiple roles during excitotoxicity. NO is produced both in neurons (blue) and in microglia (green). NO can diffuse across the membrane, and either interacts with superoxide species to create ONOO– or disrupts the BBB (pink). Extracellular ONOO– can cause lipid peroxidation or cause nTyr formation on cell membrane proteins. Alternatively, ONOO– can be formed intracellularly in neurons, by activation of the NMDAR through glutamate, where it can act as a potent oxidant. tPA can directly mediate disruption of the BBB and/or activate microglia by interaction with extracellular annexin II. Once activated, microglia can produce additional NO to be converted to ONOO– or interact with the BBB.
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