Activation of the nuclear factor erythroid 2-related factor 2-antioxidant response element signal in rats with diffuse axonal injury.

Oxidative stress is a critical mechanism underlying secondary injury during diffuse axonal injury (DAI), and nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) is an important element in the antioxidative stress pathway. This study investigated changes in Nrf2-ARE expression in rats with DAI to provide a basis for studying the DAI mechanism and a guide for clinical practice. The rat traumatic brain injury (TBI) model was established by a speeding rotation device and confirmed by neural scoring and silver staining. Nrf2 protein expression at 1, 6, 24, 48, and 72 h after TBI was measured by western blot analysis. Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 gene expression was measured by RT-PCR. The in-situ expression of Nrf2 and HO-1 was detected by immunohistochemistry analysis. Nrf2 protein expression was significantly higher in TBI rats than in sham rats (P<0.01). The change in Nrf2 expression was time dependent, peaking at 24 h and remaining high for 72 h. RT-PCR analysis indicated that HO-1 and NAD(P)H:quinone oxidoreductase 1 mRNA expression was increased in TBI rats compared with that in sham rats (P<0.05). Immunohistochemistry analysis indicated that the Nrf2 and HO-1 expression in the nuclei and cytoplasm of neurons and glial cells was significantly increased in TBI rats compared with that in sham rats (P<0.05). The Nrf2-ARE signaling pathway may be involved in the endogenous response to DAI.