Traumatic spinal cord injury induces nuclear factor-κB activation

John R. Bethea, Marcia Castro, Robert Keane, Thomas T. Lee, W. Dalton Dietrich, Robert P. Yezierski

Research output: Contribution to journalArticle

389 Citations (Scopus)

Abstract

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-κB (NF-κB) 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- κB 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-κB was evaluated by using a monoclonal antibody that selectively recognizes activated p65 in a NF-κB dimer. Immunohistochemical and Western blot analyses demonstrated that NF-κB 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-κB is activated after SCI. In our immunohistochemical, Western, and EMSA experiments there are detectable levels of activated NF-κB in our control animals. Using double-staining protocols, we detected activated NF-κB in macrophages/microglia, endothelial cells, and neurons within the injured spinal cord. Colocalization of activated NF-κB with the NF-κB-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-κB after trauma. Strategies directed at blocking the initiation of this cascade may prove beneficial as a therapeutic approach for the treatment of acute SCI.

Original languageEnglish
Pages (from-to)3251-3260
Number of pages10
JournalJournal of Neuroscience
Volume18
Issue number9
StatePublished - May 1 1998

Fingerprint

Spinal Cord Injuries
Electrophoretic Mobility Shift Assay
Wounds and Injuries
Transcription Factors
Contusions
Microglia
Nitric Oxide Synthase Type II
Transcriptional Activation
Genes
Spinal Cord
Cell Death
Endothelial Cells
Western Blotting
Macrophages
Monoclonal Antibodies
Staining and Labeling
Inflammation
Neurons

Keywords

  • CNS
  • EMSA
  • Inflammation
  • Nitric oxide synthase
  • Nuclear factor-κB
  • Secondary injury
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bethea, J. R., Castro, M., Keane, R., Lee, T. T., Dalton Dietrich, W., & Yezierski, R. P. (1998). Traumatic spinal cord injury induces nuclear factor-κB activation. Journal of Neuroscience, 18(9), 3251-3260.

Traumatic spinal cord injury induces nuclear factor-κB activation. / Bethea, John R.; Castro, Marcia; Keane, Robert; Lee, Thomas T.; Dalton Dietrich, W.; Yezierski, Robert P.

In: Journal of Neuroscience, Vol. 18, No. 9, 01.05.1998, p. 3251-3260.

Research output: Contribution to journalArticle

Bethea, JR, Castro, M, Keane, R, Lee, TT, Dalton Dietrich, W & Yezierski, RP 1998, 'Traumatic spinal cord injury induces nuclear factor-κB activation', Journal of Neuroscience, vol. 18, no. 9, pp. 3251-3260.
Bethea, John R. ; Castro, Marcia ; Keane, Robert ; Lee, Thomas T. ; Dalton Dietrich, W. ; Yezierski, Robert P. / Traumatic spinal cord injury induces nuclear factor-κB activation. In: Journal of Neuroscience. 1998 ; Vol. 18, No. 9. pp. 3251-3260.
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