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Evidence for the role of PPAR‐β/δ in the development of spinal cord injury
Author(s) -
Esposito Emanuela,
Paterniti Irene,
Mazzon Emanuela,
Genovese Tiziana,
Galuppo Maria,
Di Paola Rosanna,
Bramanti Placido,
Kapoor Amar,
Thiemermann Christoph,
Cuzzocrea Salvatore
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb461
Subject(s) - spinal cord , spinal cord injury , laminectomy , agonist , medicine , inflammation , tunel assay , nitrotyrosine , peroxisome proliferator activated receptor , endocrinology , apoptosis , oxidative stress , receptor , anesthesia , chemistry , nitric oxide synthase , nitric oxide , immunohistochemistry , biochemistry , psychiatry
Evidence suggests a biological role for peroxisome proliferator activated receptor (PPAR)‐β/δ in the pathogenesis of a number of diseases. The aim of the present study was to evaluate the contribution of PPAR‐β/δ in the secondary damage following experimental 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 resulted in severe trauma characterized by oedema, neutrophil infiltration, production of inflammatory mediators, tissue damage, and apoptosis. The high affinity PPAR‐β/δ agonist GW0742 (0.3 mg/kg, i.p.) 1 and 6 h after the SCI significantly reduced: (1) the degree of spinal cord inflammation and tissue injury, (2) neutrophil infiltration, (3) nitrotyrosine formation, (4) pro‐inflammmaory cytokines, (5) NF‐κB activation, (6) iNOS expression and (6) apoptosis (TUNEL staining, FasL, Bax and Bcl‐2 expression). Moreover, GW0742 significantly ameliorated the recovery of locomotory function (evaluated by motor score). In order to elucidate whether the protective effects of GW0742 are related to activation of the PPAR‐β/δ, we investigated the function of PPAR‐β/δ antagonist, GSK0660, on the protective effects of GW0742. GSK0660 (1 mg/kg i.p. 30 min prior to GW0742)significantly blunted the protective effect of the PPAR‐β/δ agonist. Our results demonstrate that GW0742 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.