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

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-a ligand in an experimental model of spinal cord trauma. Spinal cord injury was induced in PPAR-a 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-alpha KO 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-alpha KO 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. (c) 2005 Elsevier Inc. All rights reserved.