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The Journal of Neuroscience, May 1, 1998, 18(9):3251-3260

Traumatic Spinal Cord Injury Induces Nuclear Factor-B Activation

John R. Bethea^{1, 2}, Marcia Castro¹, Robert W. Keane³, Thomas T. Lee², W. Dalton Dietrich^{1, 2}, and Robert P. Yezierski^{1, 2}

¹ The Miami Project to Cure Paralysis, and the Departments of ² Neurological Surgery and ³ Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136

Inflammatory responses are a major component of secondary injury and play a central role in mediating the pathogenesis of acute and chronic spinal cord injury (SCI). The nuclear factor-B (NF-B) family of transcription factors is required for the transcriptional activation of a variety of genes regulating inflammatory, proliferative, and cell death responses of cells. In this study we examined the temporal and cellular expression of activated NF-B after traumatic SCI. We used a contusion model (N.Y.U. Impactor) to initiate the early biochemical and molecular changes that occur after traumatic injury to reproduce the pathological events associated with acute inflammation after SCI. The activation and cellular distribution of activated NF-B was evaluated by using a monoclonal antibody that selectively recognizes activated p65 in a NF-B dimer. Immunohistochemical and Western blot analyses demonstrated that NF-B activation occurred as early as 0.5 hr postinjury and persisted for at least 72 hr. Using electrophoretic mobility shift assays (EMSA), we demonstrate that NF-B is activated after SCI. In our immunohistochemical, Western, and EMSA experiments there are detectable levels of activated NF-B in our control animals. Using double-staining protocols, we detected activated NF-B in macrophages/microglia, endothelial cells, and neurons within the injured spinal cord. Colocalization of activated NF-B with the NF-B-dependent gene product, inducible nitric oxide synthase (iNOS), suggests functional implications for this transcription factor in the pathogenesis of acute spinal cord injury. Although there is considerable evidence for the involvement of an inflammatory reaction after traumatic SCI, this is the first evidence for the activation of NF-B after trauma. Strategies directed at blocking the initiation of this cascade may prove beneficial as a therapeutic approach for the treatment of acute SCI.

Key words: nuclear factor-B; spinal cord injury; inflammation; secondary injury; nitric oxide synthase; CNS; EMSA

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1893251-10$05.00/0

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