Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma

Background: palmitoylethanolamide (pea) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. moreover,several data have suggested that pea reduced inflammation and tissue injury associated with spinal cord trauma and showed a regulatory role for peroxisome proliferator-activated receptor (ppar)-α signaling in the neuroprotective effect of pea. however,several other mechanisms could explain the anti-inflammatory and anti-hyperalgesic effects of pea,including the activation of ppar-δ and ppar-γ. the aim of the present study was to carefully investigate the exact contribution of ppar-δ and ppar-γ in addition to ppar-α,in the protective effect of pea on secondary inflammatory damage associated with an experimental model of spinal cord injury (sci).methods: sci was induced in mice through a spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level t5 to t8 laminectomy,and pea (10 mg/kg,intraperitoneally,1 and 6 hours after sci) was injected into wildtype mice and into mice lacking ppar-α (ppar-αko). to deepen the ability of specific ppar-δ and ppar-γ antagonists to reverse the effect of pea,mice were administered gsk0660 or gw9662,30 minutes before pea injection.results: genetic ablation of ppar-α in mice exacerbated spinal cord damage,while pea-induced neuroprotection seemed be abolished in pparαko mice. twenty-four hours after spinal cord damage,immunohistological and biochemical studies were performed on spinal cord tissue. our results indicate that ppar-δ and ppar-γ also mediated the protection induced by pea. in particular,pea was less effective in ppar-αko,gsk0660-treated or gw9662-pretreated mice,as evaluated by the degree of spinal cord inflammation and tissue injury,neutrophil infiltration,proinflammmatory cytokine,inducible nitric oxide synthase expression and motor function. pea is also able to restore ppar-δ and ppar-γ expression in spinal cord tissue.conclusion: this study indicates that ppar-δ and ppar-γ can also contribute to the anti-inflammatory activity of pea in sci. © 2013 paterniti et al.; licensee biomed central ltd.