Methylprednisolone inhibition of TNF-α expression and NF-κB activation after spinal cord injury in rats

Jan Xu, Guangshun Fan, Shawei Chen, Yingji Wu, Xiao Ming Xu, Chung Y. Hsu

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

Post-traumatic inflammatory reaction has been implicated in the secondary injury after SCI. TNF-α is a key inflammatory mediator, which plays a pathogenetic role in cell death in inflammatory disorders and traumatic brain injury. TNF-α exerts its effector actions, at least partially, through the activation of a pro-inflammatory transcription factor, NF-κB, which in turn upregulates such genes as iNOS, cytokines, adhesive molecules, and others. Consistent with a post-traumatic inflammatory reaction after SCI, we noted an increase in TNF-α expression by Western blotting (4.5-fold increase at 1 day after SCI, P < 0.01) and immunohistochemistry in a rat SCI model. Post-traumatic TNF-α expression was accompanied by an increase in NF-κB binding activity in nuclear proteins isolated from the injured cord (3.9-fold increase, P < 0.01). MP is the only drug proven effective in improving neurological function in patients with acute SCI. The mechanism of action of MP is not fully understood, but is thought to be related to its antioxidant effects. MP is also a potent anti-inflammatory agent, which has been recently shown to inhibit NF-κB binding activity. MP (30 mg/kg, i.v.) given immediately after SCI reduced TNF-α expression by 55% (P < 0.01) and NF-κB binding activity. These findings suggest that post-traumatic inflammatory activity that is mediated by the TNF-α-NF-κB cascade can be suppressed by MP.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalMolecular Brain Research
Volume59
Issue number2
DOIs
StatePublished - Aug 31 1998
Externally publishedYes

Keywords

  • Cytokine
  • Gene expression
  • Inflammation
  • Secondary injury
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Methylprednisolone inhibition of TNF-α expression and NF-κB activation after spinal cord injury in rats'. Together they form a unique fingerprint.

Cite this