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Effect of cyclopentanone prostaglandin 15-deoxy-delta12,14PGJ2 on early functional recovery from experimental spinal cord injury.
Shock. 2008 Aug; 30(2):142-52.S

Abstract

Peroxisome proliferator-activated receptor (PPAR) gamma 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-DeltaPGJ2 (15d-PGJ2), which is a metabolite of the prostaglandin D2, functions as an endogenous ligand for PPAR-gamma 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-kappaB activation, (4) expression of iNOS, nitrotyrosine and TNF-alpha, 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-gamma receptor, we also investigated the effect of a PPAR-gamma 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-gamma 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.

Authors+Show Affiliations

IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18628687

Citation

Genovese, Tiziana, et al. "Effect of Cyclopentanone Prostaglandin 15-deoxy-delta12,14PGJ2 On Early Functional Recovery From Experimental Spinal Cord Injury." Shock (Augusta, Ga.), vol. 30, no. 2, 2008, pp. 142-52.
Genovese T, Esposito E, Mazzon E, et al. Effect of cyclopentanone prostaglandin 15-deoxy-delta12,14PGJ2 on early functional recovery from experimental spinal cord injury. Shock. 2008;30(2):142-52.
Genovese, T., Esposito, E., Mazzon, E., Di Paola, R., Muià, C., Meli, R., Bramanti, P., & Cuzzocrea, S. (2008). Effect of cyclopentanone prostaglandin 15-deoxy-delta12,14PGJ2 on early functional recovery from experimental spinal cord injury. Shock (Augusta, Ga.), 30(2), 142-52. https://doi.org/10.1097/SHK.0b013e31815dd381
Genovese T, et al. Effect of Cyclopentanone Prostaglandin 15-deoxy-delta12,14PGJ2 On Early Functional Recovery From Experimental Spinal Cord Injury. Shock. 2008;30(2):142-52. PubMed PMID: 18628687.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of cyclopentanone prostaglandin 15-deoxy-delta12,14PGJ2 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 - 2008/7/17/pubmed PY - 2008/9/24/medline PY - 2008/7/17/entrez SP - 142 EP - 52 JF - Shock (Augusta, Ga.) JO - Shock VL - 30 IS - 2 N2 - Peroxisome proliferator-activated receptor (PPAR) gamma 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-DeltaPGJ2 (15d-PGJ2), which is a metabolite of the prostaglandin D2, functions as an endogenous ligand for PPAR-gamma 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-kappaB activation, (4) expression of iNOS, nitrotyrosine and TNF-alpha, 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-gamma receptor, we also investigated the effect of a PPAR-gamma 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-gamma 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. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/18628687/Effect_of_cyclopentanone_prostaglandin_15_deoxy_delta1214PGJ2_on_early_functional_recovery_from_experimental_spinal_cord_injury_ L2 - https://doi.org/10.1097/SHK.0b013e31815dd381 DB - PRIME DP - Unbound Medicine ER -