Expression of nuclear factor κB and tumor necrosis factor α in the mouse brain after experimental thermal ablation injury

OBJECTIVE: Nuclear factor kappa B (NF kappaB) participates in the regulation of a diverse range of genes involved in inflammation and acute phase responses. We investigated the expression of the activated form of NF kappaB and tumor necrosis factor alpha (TNF alpha), an inflammatory cytokine, in experimental brain injury. METHODS: We generated focal brain injury in mice using radiofrequency thermal ablation at the caudate putamen in mite. Intracerebral expression of INF alpha and the p50 and p65 subunits of NF kappaB were studied using immunohistochemistry at 1, 4, and 8 hours and at 1, 2, 4, 8, 14, and 28 days postinjury. RESULTS: Coagulative necrosis approximately 2 mm in diameter was produced at the site of injury. No immunoreactivity for TNF alpha, NF kappaB p50, or NF kappaB p65 was detected in the injured area in the early phase postinjury. On posttrauma Day 2, however, weak expression of TNF alpha, NF kappaB p50, and NF kappaB p65 was detected in mononuclear cells that infiltrated edematous tissue surrounding the lesion. On posttrauma Days 4 to 8, the expression of TNF alpha, NF kappaB p50, and NF kappaB p65 was prominently increased in infiltrating and proliferating mononuclear cells (macrophages and microglia) and in proliferating reactive astrocytes surrounding the lesion. Nuclear subcellular localization of the expression of NF kappaB p50 and p65 was observed, which indicated that these subunits might be activated in these cells. On posttrauma Day 1 4, the expression of TNF alpha, NF kappaB p50, and NF kappaB p65 decreased and was limited to mononuclear cells, and it finally disappeared on Day 28. The temporal profiles of TNF alpha, NF kappaB p50, and NF kappaB p65 were closely associated with the occurrence of secondary insults and the tissue-remodeling process in wound healing. CONCLUSION: These results suggest that TNF alpha, NF kappaB p50, and NF kappaB p65 may play a central role in the injury-induced immune response that leads to secondary insults or wound healing after brain injury. Inappropriate and deregulated activation of NF kappaB in injured brain tissue may be implicated in the development of secondary brain damage.