Effects of a metalloporphyrinic peroxynitrite decomposition catalyst, ww-85, in a mouse model of spinal cord injury

Tiziana Genovese, Emanuela Mazzon, Emanuela Esposito, Rosanna Di Paola, Kanneganti Murthy, Lewis Neville, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

The aim of the present study was to assess the effect of a metalloporphyrinic peroxynitrite decomposition catalyst, ww-85, in the pathophysiology of spinal cord injury (SCI) in mice. Spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by oedema, neutrophil infiltration, production of inflammatory mediators, tissue damage and apoptosis. ww-85 treatment (30-300 μg/kg, i.p. 1 h after the SCI) significantly reduced in a dose-dependent manner: (1) the degree of spinal cord inflammation and tissue injury, (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation and PARP activation, (4) pro-inflammatory cytokines expression, (5) NF-κB activation and (6) apoptosis. Moreover, ww-85 significantly ameliorated the recovery of limb function (evaluated by motor recovery score) in a dose-dependent manner. The results demonstrate that ww-85 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Original languageEnglish
Pages (from-to)631-645
Number of pages15
JournalFree Radical Research
Volume43
Issue number7
DOIs
Publication statusPublished - 2009

Keywords

  • Peroxynitrite
  • Spinal cord injury
  • ww-85

ASJC Scopus subject areas

  • Biochemistry

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