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

Exp Neurol. 2005 Jul;194(1):267-78. doi: 10.1016/j.expneurol.2005.03.003.


The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) 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-alpha ligand in an experimental model of spinal cord trauma. Spinal cord injury was induced in PPAR-alpha wild-type (WT) mice and PPAR-alpha knock out mice (PPAR-alpha 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-alpha was observed in the spinal cord of spinal cord-injured PPAR-alpha WT mice. Absence of a functional PPAR-alpha gene in PPAR-alphaKO 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-alpha gene in PPAR-alphaKO mice significantly worsened the recovery of limb function (evaluated by motor recovery score). Thus, endogenous PPAR-alpha ligands reduce the degree of development of inflammation and tissue injury events associated with spinal cord trauma in the mice.

MeSH terms

  • Age Factors
  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • Neutrophils / pathology
  • PPAR alpha / genetics*
  • PPAR alpha / metabolism*
  • Peroxynitrous Acid / metabolism
  • Severity of Illness Index
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology*
  • Spinal Cord Injuries / immunology
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • Tumor Necrosis Factor-alpha / metabolism


  • Ligands
  • PPAR alpha
  • Tumor Necrosis Factor-alpha
  • Peroxynitrous Acid