title: Effects of combination of melatonin and dexamethasone on secondary injury in an experimental mice model of spinal cord trauma.
abstract: This study investigates the effects of combination therapy with melatonin and dexamethasone on the degree of spinal cord injury caused by the application of vascular clip in mice. Spinal cord injury in mice resulted in severe trauma, characterized by edema, neutrophil infiltration, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and immunoreaction of Bax, Bcl-2, and Fas Ligand). Infiltration of the spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced immuno- histochemical and functional alterations revealed, respectively, by an increased of tumor necrosis factor (TNF)-alpha immunoreactivity, NOS as well as nitrotyrosine and loss of hind leg movement in spinal cord injury (SCI)-operated mice. In contrast, the degree of neutrophil infiltration at different time points, cytokine expression, histologic damage iNOS expression, apoptosis, was markedly reduced in the tissues obtained from SCI-treated mice with the combination therapy, and the motor recovery was also ameliorated. No anti-inflammatory effect was observed in animals treated with melatonin (10 mg/kg) or with dexamethasone (0.025 mg/kg) alone. This study shows that the combination therapy with melatonin and dexamethasone reduces the degree of secondary damage associated with spinal cord injury in mice, and supports the possible use of melatonin in combination with steroids to reduce the dose and the side effects related with the use of steroids for the management of inflammatory disease.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Carmelo
authors.initials: C
authors.lastname: Muià
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Bella
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin