Nrf2-ARE pathway has been proved to be the key regulator in reducing oxidative stress, inflammatory damage, and accumulation of toxic metabolites, which are all involved in TBI. Our previous study has proved the augmentation of Nrf2 in brain tissue after TBI [17]. Enhanced level of Nrf2 activates transcription of a group of antioxidant genes, such as heme oxygenase-1 (HO-1) and NAD (P)H: quinone oxidoreductase-1 (NQO1), which would subsequently reduce the damage in brain [18]. Postinjury administration of SFN, an inducer of Nrf2, significantly improves spatial memory of rat and decreases the immunoreactivity for 4-Hydroxynonenal (4-HNE), a marker of lipid peroxidation, in the cortex and the CA3 subfield of hippocampus after TBI [19]. On the other hand, Nrf2-deficient mice appear more susceptible to TBI. Depletion of Nrf2 induces higher expression of proinflammatory mediators in brain after TBI [20]. Here, our results revealed that overexpression of TNF-α, IL-1β, IL-6, and MMP9 after scratch injury was more aggravated in cultured Nrf2 knockout astrocytes than in wildtype astrocyetes for the first time, and overexpression of these proinflammatory mediators led to more astrocytes deaths.