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.