Regulatory Role of NADPH Oxidase 2 in the Polarization Dynamics and Neurotoxicity of Microglia/Macrophages after Traumatic Brain Injury.

Regulatory Role of NADPH Oxidase 2 in the Polarization Dynamics and Neurotoxicity of Microglia/Macrophages after Traumatic Brain Injury. Free Radic Biol Med. 2017 Sep 20;: Authors: Wang J, Ma MW, Dhandapani KM, Brann DW Abstract Traumatic brain injury (TBI) is a leading cause of death and disability. Secondary injuries that develop after the initial trauma contribute to long-lasting neurophysiological deficits. Polarization of microglia/macrophages toward a pro-inflammatory (M1) phenotype may increase the progression of secondary injury following TBI; however, the regulatory and functional mechanisms underlying these changes remain poorly defined. In the present study, we showed elevated expression of NADPH oxidase 2 (NOX2) and activation of nuclear factor-kappa B (NF-κB) predominantly in microglia/macrophages at 4- and 7-days after controlled cortical impact in mice. Delayed inhibition of NOX2, beginning one day after TBI, reduced reactive oxygen species production of myeloid cells and protected neurons from oxidative damage. Moreover, delayed NOX inhibition or global genetic NOX2 knockout suppressed the M1 "pro-inflammatory" profile of microglia/macrophages and simultaneously increased the M2 "anti-inflammatory" profile in the injured brain. These changes were associated with marked down-regulation of the NF-κB pathway in microglia/macrophages and reduced production of pro-inflammatory cytokines, tumor necrosis factor-α and inte...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research