• Emanuela Esposito, Irene Paterniti, Rosaria Meli, Placido Bramanti, and Salvatore Cuzzocrea.
• Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
• Spine. 2012 Jan 15; 37 (2): E73-8.

Study DesignExperimental study of spinal cord injury (SCI) using an organotypic slice culture.ObjectiveTo clarify the protective mechanism of PPAR-δ agonist GW0742 in the injured spinal cord using an in vitro model.Summary Of Background DataIn 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 disease also have shown neuroprotection conferred by PPAR-δ. The biological role and function of PPAR-δ remains relatively unclear.MethodsSpinal 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 at 1 hour before injury.ResultsOur study shows that GW0742 incubation (10 μM) at 1 hour 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.ConclusionGW0742 reduces the cellular and molecular changes occurring in SCI by targeting different downstream pathways modulating PPAR-δ receptors.

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