TNF-alpha blockage in a mouse model of SCI: evidence for improved outcome

Shock. 2008 Jan;29(1):32-41. doi: 10.1097/shk.0b013e318059053a.


The aim of our study was to evaluate in vivo the therapeutic efficacy of genetic inhibition of TNF-alpha using TNF-R1 knockout mice in an experimental model of spinal cord trauma. Spinal cord injury was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. To elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-alpha, we also investigated the effect of infliximab, a TNF-alpha-soluble receptor construct, on spinal cord damage. Pharmacological and genetic TNF-alpha inhibition significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (evaluated by myeloperoxidase activity), (3) cytokine expression (TNF-alpha), (4) and apoptosis (terminal deoxynucleotidyltransferase-mediated uridine triphosphate end labeling staining, Bax, Bcl-2, and Fas-L expression). In a separate set of experiments, we have also demonstrated that TNF-alpha inhibition significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that inhibition of TNF-alpha reduces the development of inflammation and tissue injury associated with spinal cord trauma, suggesting a possible role of TNF-alpha on the pathogenesis of spinal cord injury.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Fas Ligand Protein / metabolism
  • Infliximab
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Knockout
  • Models, Neurological
  • Neutrophils / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Tumor Necrosis Factor, Type I / deficiency
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism


  • Antibodies, Monoclonal
  • Bax protein, mouse
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Interleukin-1beta
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Tumor Necrosis Factor, Type I
  • Tnfrsf1a protein, mouse
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Infliximab
  • Casp3 protein, mouse
  • Caspase 3