TNF-α blockage in a mouse model of SCI: Evidence for improved outcome

Tiziana Genovese, Emanuela Mazzon, Concetta Crisafulli, Rosanna Di Paola, Carmelo Muià, Emanuela Esposito, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

The aim of our study was to evaluate in vivo the therapeutic efficacy of genetic inhibition of TNF-α 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-α, we also investigated the effect of infliximab, a TNF-α-soluble receptor construct, on spinal cord damage. Pharmacological and genetic TNF-α 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-α), (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-α inhibition significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that inhibition of TNF-α reduces the development of inflammation and tissue injury associated with spinal cord trauma, suggesting a possible role of TNF-α on the pathogenesis of spinal cord injury.

Original languageEnglish
Pages (from-to)32-41
Number of pages10
JournalShock
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • Apoptosis
  • Cytokine expression
  • Neutrophil infiltration
  • Trauma

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

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    Genovese, T., Mazzon, E., Crisafulli, C., Di Paola, R., Muià, C., Esposito, E., Bramanti, P., & Cuzzocrea, S. (2008). TNF-α blockage in a mouse model of SCI: Evidence for improved outcome. Shock, 29(1), 32-41. https://doi.org/10.1097/shk.0b013e318059053a