Reduced Oxidative Stress Promotes NF-κB-Mediated Neuroprotective Gene Expression after Transient Focal Cerebral Ischemia: Lymphocytotrophic Cytokines and Antiapoptotic Factors

Abstract

Nuclear factor-kappa B (NF-κB) is activated by oxidative stress such as that induced by transient focal cerebral ischemia (tFCI). Whether NF-κB has a role in cell survival or death in stroke is a matter of debate. We proposed that the status of oxidative stress may determine its role in cell death or survival after focal ischemia. To characterize the coordinated expression of genes in NF-κB signaling after mild cerebral ischemia, we investigated the temporal profile of a NF-κB-pathway-focused DNA array after 30 mins of tFCI in wild-type (WT) mice and human copper/zinc-superoxide dismutase transgenic (SOD1 Tg) mice that had a significantly reduced level of superoxide. Differentially expressed genes among 96 NF-κB-related genes were further confirmed and compared in the WT and SOD1 Tg mice using quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. Persistent upregulation of NF-κB seen at 7 days in the WT mice was decreased in the SOD1 Tg mice. Lymphocytotrophic cytokine genes such as interleukin-2, interleukin-12, and interferon-α1 were increased in the SOD1 Tg mice compared with the WT mice after tFCI. In addition, antiapoptosis factors bcl-2 and tumor necrosis factor receptor-associated factor 1 rapidly increased in the SOD1 Tg mice compared with the WT mice. This study indicates that reduced oxidative stress by SOD1 overexpression increased NF-κB-related rapid defenses, such as immune response and antiapoptosis factors, and prevented brain damage after tFCI-induced oxidative stress.