Regulation of NADPH oxidase gene: the role and meaning as a therapeutic target in septic encephalopathy.

We focused on NADPH oxidase (Nox) activity and studied about sepsis encephalopathy. Proinflammatory cytokines and brain vessel permeability were significantly up-regulated in septic mice brain. And, Nox subunits, p47phox and p67phox, oxidative stress marker 8-OHdG, and iNOS expression were up-regulated in septic brains. These indicate that superoxide, produced by Nox, reacts with NO to form peroxynitrite, that might provoke a failed blood brain barrier. Light and electron microscopic examination showed that serious neuronal degeneration was occurred in septic mice brain. However, these histopathological changes were mitigated by treatment with the free radical scavenger edaravone. Thus, it was suggested that Nox gene might be therapeutic target for treating septic encephalopathy.