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GW0742, A High Affinity Ppar-δ Gonist, Mediates Protection in an Organotypic Model of Spinal Cord Damage.
MedLine Citation:
PMID:  21685825     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Study Design. Experimental study of spinal cord injury using an organotypic slice culture.Objective. To clarify the protective mechanism of PPAR-δ agonist GW0742 in the injured spinal cord using an in-vitro model.Summary of Background Data. In vivo data suggest that ligands of the δ isoform have activity in a number of disease models that are partly driven by the inflammatory response. Moreover, reports from in vivo studies using models of ischemia reperfusion and Parkinson's disease also have shown neuroprotection conferred by PPAR-δ. The biological role and function of PPAR-δ remains relatively unclear.Methods. Spinal cord from 6-week-old mice was cut into transverse slices of 400 μm thickness to generate the organotypic slice cultures. The slices were injured using a weight dropped onto the center of the slice. PPAR-δ agonist was applied at 10 μM 1 h before injuryResults. Our study shows that GW0742 incubation (10 μM) 1 h before transverse lesion significantly reduced: (1) p38 mitogen-activated protein kinase (MAPK), (2) c-Jun N-Terminal Kinase (JNK/SAP Kinase), (3) NF-κB activation, (4) loss of neurotrophic factors (BDNF, GDNF), (5) COX-2 expression and (6) cell death.Conclusion. GW0742 reduces the cellular and molecular changes occurring in spinal cord injury by targeting on different downstream pathway modulating PPARδ receptor.
Authors:
Emanuela Esposito; Irene Paterniti; Rosaria Meli; Placido Bramanti; Salvatore Cuzzocrea
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-16
Journal Detail:
Title:  Spine     Volume:  -     ISSN:  1528-1159     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7610646     Medline TA:  Spine (Phila Pa 1976)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy †IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy ‡Dipartimento di Farmacologia Sperimentale, Università di Napoli "Federico II", Italy.
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