Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury.
Activation of peroxisome proliferator-activated receptor (PPAR)-alpha, 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-alpha 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 T(5)-T(8) 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-kappaB 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-alpha signaling in the inflammatory response associated with spinal cord trauma.
Genovese
Tiziana
T
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Esposito
Emanuela
E
Mazzon
Emanuela
E
Di Paola
Rosanna
R
Meli
Rosaria
R
Bramanti
Placido
P
Piomelli
Daniele
D
Calignano
Antonio
A
Cuzzocrea
Salvatore
S
D000577:Amides; D000818:Animals; D063388:Endocannabinoids; D004983:Ethanolamines; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D010169:Palmitic Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013904:Thoracic Vertebrae / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000577:Amides; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; C005958:palmidrol; D052247:Nitric Oxide Synthase Type II