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-kappa 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-kappa B). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), 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-kappa B activation, inflammatory cytokines TNF-alpha, IL-1 beta 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-kappa B activity, proinflammatory cytokine, and ICAM-1 after TBI. Copyright (c) 2008 Wei Jin et al.