Deletion of Nrf2 Exacerbates Oxidative Stress After Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) is a worldwide public health and medical problem. Oxidative stress is recognized as an important contributing factor in the pathogenesis of TBI. The present study was designed to explore the anti-oxidative effect of Nuclear factor erythroid 2-related factor 2 (Nrf2) on brain damage induced by traumatic injury in a mouse model. Moderate weight-drop impact head injury was induced in adult male mice. The mice were randomly divided into four groups: Nrf2+/+ sham-operation, Nrf2−/− sham-operation, Nrf2+/+ TBI, and Nrf2−/− TBI group. Neurological scores were evaluated 24 h after TBI, followed by collection of the brain specimens. Brain edema was detected by the wet−dry ratio method. The expression of NOX2 protein in the brain specimen was investigated using Western Blot analysis and immunohistochemical staining. In addition, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were evaluated in the brain tissues. Twenty-four hours after TBI, our results showed Nrf2+/+ TBI mice have more severe neurological deficits and brain edema than Nrf2+/+ sham group. On the other hand, the Nrf2−/− TBI mice were found to have significantly increased neurological deficits and brain edema, compared to Nrf2+/+ TBI mice (P < 0.05). At the same time, we found that the expression of NOX2 protein, MDA level were significantly increased in Nrf2−/− mice, while SOD activity was considerably decreased after TBI compared to Nrf2+/+ mice (P < 0.05). We demonstrated that deletion of Nrf2 exacerbates brain injury after TBI in mice, suggesting that Nrf2 may play an important role in protecting brain injury after TBI, possibly by modulating oxidative stress.