NOX inhibition reduces microglial activation and toxicity. BV2 microglial cells incubated with PMA or LPS showed an increase in ROS production (A). Pre-incubation with the NOX2 specific inhibitor gp91ds-tat (10 μM), or the NOX non-specific inhibitor DPI (10 μM), significantly reduced the ROS production induced by PMA and LPS, respectively (A). LPS also induced NO• release from BV2 cells, which was inhibited by gp91-ds-tat (10 μM) and in a dose-dependent fashion by DPI (B). Co-culture of oligodendrocytes with LPS-stimulated BV2 cells for 24 hours resulted in a significant increase in oligodendrocyte cell death, as measured by LDH release (C). Pre-treatment of BV2 cells with DPI (10 μM) for 1 hour prior to LPS administration blocked this toxic effect. Bars represent mean ± SD. *P <0.05; **P <0.01; ***P <0.001.