TY - JOUR
T1 - Effect of cyclopentanone prostaglandin 15-deoxy-δ12,14PGJ2 on early functional recovery from experimental spinal cord injury
AU - Genovese, Tiziana
AU - Esposito, Emanuela
AU - Mazzon, Emanuela
AU - Di Paola, Rosanna
AU - Muià, Carmelo
AU - Meli, Rosaria
AU - Bramanti, Placido
AU - Cuzzocrea, Salvatore
PY - 2008/8
Y1 - 2008/8
N2 - Peroxisome proliferator-activated receptor (PPAR) γ is a member of the nuclear-receptor superfamily that binds to DNA with retinoid X receptors as PPAR-retinoid X receptor heterodimers. Recent evidence also suggests that the cyclopentenone prostaglandin 15-deoxy-δPGJ2 (15d-PGJ2), which is a metabolite of the prostaglandin D2, functions as an endogenous ligand for PPAR-γ We postulated that 15d-PGJ2 would attenuate inflammation, investigating the effects on the degree of experimental spinal cord trauma induced 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, production of a range of inflammatory mediators, tissue damage, and apoptosis. Furthermore, 15d-PGJ2 reduced (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) nuclear factor-κB activation, (4) expression of iNOS, nitrotyrosine and TNF-α, and (5) apoptosis (terminal deoxynucleotidyltransferase-mediated uridine triphosphate end labeling staining, Bax, Bcl-2, and FAS-L expression). In a separate set of experiments, 15d-PGJ2 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). To elucidate whether the protective effects of 15d-PGJ2 are related to activation of the PPAR-γ receptor, we also investigated the effect of a PPAR-γ antagonist, GW 9662, on the protective effects of 15d-PGJ2. GW9662 (1 mg/kg administered i.p. 30 min before treatment with 15d-PGJ2) significantly antagonized the effect of the PPAR-γ agonist and, thus, abolished the protective effect. Taken together, our results clearly demonstrate that treatment with 15d-PGJ2 reduces the development of inflammation and tissue injury associated with spinal cord trauma.
AB - Peroxisome proliferator-activated receptor (PPAR) γ is a member of the nuclear-receptor superfamily that binds to DNA with retinoid X receptors as PPAR-retinoid X receptor heterodimers. Recent evidence also suggests that the cyclopentenone prostaglandin 15-deoxy-δPGJ2 (15d-PGJ2), which is a metabolite of the prostaglandin D2, functions as an endogenous ligand for PPAR-γ We postulated that 15d-PGJ2 would attenuate inflammation, investigating the effects on the degree of experimental spinal cord trauma induced 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, production of a range of inflammatory mediators, tissue damage, and apoptosis. Furthermore, 15d-PGJ2 reduced (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) nuclear factor-κB activation, (4) expression of iNOS, nitrotyrosine and TNF-α, and (5) apoptosis (terminal deoxynucleotidyltransferase-mediated uridine triphosphate end labeling staining, Bax, Bcl-2, and FAS-L expression). In a separate set of experiments, 15d-PGJ2 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). To elucidate whether the protective effects of 15d-PGJ2 are related to activation of the PPAR-γ receptor, we also investigated the effect of a PPAR-γ antagonist, GW 9662, on the protective effects of 15d-PGJ2. GW9662 (1 mg/kg administered i.p. 30 min before treatment with 15d-PGJ2) significantly antagonized the effect of the PPAR-γ agonist and, thus, abolished the protective effect. Taken together, our results clearly demonstrate that treatment with 15d-PGJ2 reduces the development of inflammation and tissue injury associated with spinal cord trauma.
KW - Apoptosis
KW - Inflammation
KW - PPAR-γ spinal cord injury
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UR - http://www.scopus.com/inward/citedby.url?scp=52149113573&partnerID=8YFLogxK
U2 - 10.1097/SHK.0b013e31815dd381
DO - 10.1097/SHK.0b013e31815dd381
M3 - Article
C2 - 18628687
AN - SCOPUS:52149113573
VL - 30
SP - 142
EP - 152
JO - Shock
JF - Shock
SN - 1073-2322
IS - 2
ER -