Role of endogenous ligands for the peroxisome proliferators activated receptors alpha in the secondary damage in experimental spinal cord trauma

Tiziana Genovese, Emanuela Mazzon, Rosanna Di Paola, Giuseppe Cannavò, Carmelo Muià, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

The peroxisome proliferator-activated receptor-α (PPAR-α) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study was to examine the effects of endogenous PPAR-α ligand in an experimental model of spinal cord trauma. Spinal cord injury was induced in PPAR-α wild-type (WT) mice and PPAR-α knock out mice (PPAR-α KO) mice by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration (measured as an increase in myeloperoxidase activity) and apoptosis (measured by Annexin 5 staining). An increase of immunoreactivity to TNF-α was observed in the spinal cord of spinal cord-injured PPAR-α WT mice. Absence of a functional PPAR-α gene in PPAR-αKO mice resulted in a significant augmentation of all the above described parameters. In a separate set of experiments, we have also demonstrated that the absence of PPAR-α gene in PPAR-αKO mice significantly worsened the recovery of limb function (evaluated by motor recovery score). Thus, endogenous PPAR-α ligands reduce the degree of development of inflammation and tissue injury events associated with spinal cord trauma in the mice.

Original languageEnglish
Pages (from-to)267-278
Number of pages12
JournalExperimental Neurology
Volume194
Issue number1
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Apoptosis
  • Cytokines
  • Motor recovery
  • Neutrophils infiltration
  • PPAR-α ligands
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology

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