Aim: Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play a crucial role in protection against TBI induced inflammatory response in the brain. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect mice brain against TBI-induced inflammatory damage.
Methods: Adult male ICR mice were randomly divided into three groups: (1) sham+vehicle group; (2) TBI+vehicle group; and (3) TBI+tBHQ group (n=12 per group). Closed head injury was adopted using Hall's weight-dropping method. We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by electrophoretic mobility shift assay (EMSA), concentrations of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), brain oedema by wet/dry weight method, and cortical apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis.
Results: Induction of the Nrf2 activity by tBHQ markedly decreased NF-κB activation and inflammatory cytokine production in the injured brain. Administration of tBHQ also significantly attenuated TBI-induced brain oedema and cortical apoptosis.
Conclusion: Pre-treatment with tBHQ could attenuate the cerebral inflammatory response after TBI.
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