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The oxidative stress response caused by traumatic brain injury (TBI) leads to secondary damage in the form of tissue damage and cell death. Nuclear transcription-related factor 2 (NRF2) is a key factor in the body against oxidative stress and has an important role in combating oxidative damage in TBI neurons. In the present study, we investigated whether rutaecarpine could activate the PGK1/KEAP1/NRF2 pathway to antagonize oxidative damage in TBI neurons. We performed controlled cortical impact (CCI) surgery on mice and taken H2O2 trea