title: Effects of palmitoylethanolamide on release of mast cell peptidases and neurotrophic factors after spinal cord injury.
abstract: Spinal cord injury (SCI) has a significant impact on quality of life, expectancy, and economic burden, with considerable costs associated with primary care and loss of income. The complex pathophysiology of SCI may explain the difficulty in finding a suitable therapy for limiting neuronal injury and promoting regeneration. Although innovative medical care, advances in pharmacotherapy have been limited. The aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of PEA on inflammatory reaction associated with an experimental model of SCI. The compression model induced by applying an aneurysm clip to the spinal cord in mice is closer to the human situation, since it replicates the persistence of cord compression. Spinal cord trauma was induced in mice by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. Repeated PEA administration (10 mg/kg i.p., 6 and 12 h after SCI) significantly reduced the degree of the severity of spinal cord trauma through the reduction of mast cell infiltration and activation. Moreover, PEA treatment significantly reduced the activation of microglia and astrocytes expressing cannabinoid CB(2) receptor after SCI. Importantly, the protective effect of PEA involved changes in the expression of neurotrophic factors, and in spinal cord dopaminergic function. Our results enhance our understanding about mechanisms related to the anti-inflammatory property of the PEA suggesting that this N-acylethanolamine may represent a crucial therapeutic intervention both diminishing the immune/inflammatory response and promoting the initiation of neurotrophic substance after SCI.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Maria
authors.initials: M
authors.lastname: Galuppo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001253:Astrocytes / Q000737:chemistry / Q000473:pathology; D015550:Cell Degranulation / Q000187:drug effects; D053818:Chymases / Q000378:metabolism*; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D063388:Endocannabinoids; D004983:Ethanolamines; D007796:Laminectomy; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000737:chemistry / Q000473:pathology; D009187:Myelitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010169:Palmitic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D043885:Receptor, Cannabinoid, CB2 / Q000032:analysis; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D013525:Surgical Instruments; D013904:Thoracic Vertebrae; D053802:Tryptases / Q000378:metabolism*
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D050483:Dopamine Plasma Membrane Transport Proteins; D063388:Endocannabinoids; D004983:Ethanolamines; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010169:Palmitic Acids; D043885:Receptor, Cannabinoid, CB2; C005958:palmidrol; D053818:Chymases; D053802:Tryptases