BACKGROUND: Nogo-neutralizing antibody IN-1 accelerates axon growth and enhances recovery of spinal cord function by inhibiting growth inhibitory factors. Neurotrophin-3 (NT-3)contributes to regeneration of nerve fibers in the spinal cord and motor function recovery. The combination of Nogo-neutralizing antibody IN-1 and NT-3 is hypothesized to produce better outcomes and facilitate axonal regeneration by affecting c-Fos and c-Jun protein expression. OBJECTIVE: To investigate the combined effects of Nogo-neutralizing antibody IN-1 and NT-3 on c-Fos and c-Jun protein levels in the injured spinal cord. DESIGN, TIME AND SETTING: A randomized, controlled study was performed at the Laboratory of Neuroanatomy, Xiangya Medical College, Central South University and the Central Laboratory of Third Xiangya Hospital of China from June 2005 to December 2007. MATERIALS: NT-3 (Peprotech, USA) and Nogo-neutralizing antibody IN-1 (Santa Cruz Biotechnology, USA) were used in this study. METHODS: Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of rat spinal cord, which is equivalent to the T8 level in the human spine. A total of 120 rats were equally and randomly assigned to three groups: model (0.2 μL saline), IN-1 (0.2 μL IN-1), and IN-1/NT-3 (0.2 μL IN-1 + 0.2 μL NT-3). The compounds were separately infused into transection sites on the side of head. MAIN OUTCOME MEASURES: Western blot analysis was employed to measure c-Fos and c-Jun protein expression in the injured spinal cord at 15, 30 minutes, 1, 2, 4, 6, 8, and 12 hours following surgery. RESULTS: Following spinal cord injury, c-Fos and c-Jun protein expression were increased and peaked at 4-6 hours. Following injection of IN-1 or the combination of IN-1 and NT-3, c-Fos protein expression was significantly reduced in the injured spinal cord (P < 0.05 or P < 0.01) (with the exception of the 15 minute time point). However, c-Jun protein expression was significantly increased (P < 0.05 or P < 0.01) (with the exception of the 15 and 30 minute time points). Combined application of IN-1 and NT-3 resulted in significantly altered protein expression compared to IN-1 alone. CONCLUSION: IN-1 increases c-Jun protein levels and protects the injured spinal cord by inhibiting c-Fos protein levels. Moreover, the effects of IN-1 combined with NT-3 are more significant than with IN-1 alone.