Disruption of Nrf2 Enhances Upregulation of Nuclear Factor‐κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule‐1 in the Brain after Traumatic Brain Injury

Inflammatory response plays an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in the cerebral upregulation of NF- κ B activity, proinflammatory cytokine, and ICAM-1 after TBI. Wild-type Nrf2 (+/+) and Nrf2 (−/−)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Electrophoretic mobility shift assays (EMSAs) were performed to analyze the activation of nuclear factor kappa B (NF- κ B). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ), and interleukin-6 (IL-6). Immunohistochemistry staining experiments were performed to detect the expression of intercellular adhesion molecule-1 (ICAM-1). Nrf2 (−/−) mice were shown to have more NF- κ B activation, inflammatory cytokines TNF- α , IL-1 β and IL-6 production, and ICAM-1 expression in brain after TBI compared with their wild-type Nrf2 (+/+) counterparts. The results suggest that Nrf2 plays an important protective role in limiting the cerebral upregulation of NF- κ B activity, proinflammatory cytokine, and ICAM-1 after TBI.