Tert-butylhydroquinone protects the spinal cord against inflammatory response produced by spinal cord injury

Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play an important role in protection against spinal cord injury (SCI) induced inflammatory response. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect the spinal cord against SCI-induced inflammatory damage. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. Three groups were analyzed: a sham group, a SCI group, and a SCI+rhEPO group (n=16 per group). We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by an electrophoretic mobility shift assay (EMSA). We also measured the concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay (ELISA); we also measured hindlimb locomotion function by the Basso, Beattie, and Bresnahan (BBB) rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. The results showed that the induction of the Nrf2 activity by tBHQ markedly decreased NF-κB activation and inflammatory cytokines production in the injured spinal cord. Administration of tBHQ also significantly attenuated SCI induced hindlimb locomotion deficits, spinal cord edema, and apoptosis. To conclude, pre-treatment with tBHQ could attenuate the spinal cord inflammatory response after SCI.