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-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.
Genovese
Tiziana
T
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica-Policlinico Universitario Via C. Valeria-Gazzi, 98100 Messina, Italy.
Mazzon
Emanuela
E
Di Paola
Rosanna
R
Cannavò
Giuseppe
G
Muià
Carmelo
C
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008024:Ligands; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; D030421:Peroxynitrous Acid