Abstract
Activation of peroxisome proliferator-activated receptor (PPAR)-α, a member of the nuclear receptor superfamily, modulates inflammation and tissue injury events associated with spinal cord trauma in mice. Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through a mechanism dependent on PPAR-α activation. The aim of the present study was to evaluate the effect of the PEA on secondary damage induced by experimental spinal cord injury (SCI) in mice. SCI was induced by application of vascular clips to the dura mater via a four-level T5-T8 laminectomy. This resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis. Repeated PEA administration (10 mg/kg i.p.; 30 min before and 1 and 6 h after SCI) significantly reduced: 1) the degree of spinal cord inflammation and tissue injury, 2) neutrophil infiltration, 3) nitrotyrosine formation, 4) proinflammatory cytokine expression, 5) nuclear transcription factor activation-κB activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis. Moreover, PEA treatment significantly ameliorated the recovery of motor limb function. Together, the results indicate that PEA reduces inflammation and tissue injury associated with SCI and suggest a regulatory role for endogenous PPAR-α signaling in the inflammatory response associated with spinal cord trauma.
Footnotes
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T.G. and E.E. contributed equally to this work.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.108.136903.
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ABBREVIATIONS: SCI, spinal cord injury; BBB, blood-brain barrier; PPAR, peroxisome proliferator-activated receptor; RXR, retinoid X receptor; PEA, palmitoylethanolamide; iNOS, inducible nitric-oxide synthase; NF-κB, nuclear transcription factor activation-κB; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling; MPO, myeloperoxidase activity; PBS, phosphate-buffered saline; PMSF, phenylmethylsulfonyl fluoride; TNF, tumor necrosis factor; IL, interleukin; MDA, malondialdehyde bis (dimethyl acetal); PARP, poly(ADP-ribose) polymerase; PAR, poly(ADP-ribose).
- Received January 21, 2008.
- Accepted March 25, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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