Melatonin is the principal secretory product of the pineal gland and its role as an immuno-modulator is well established. Recent evidence shows that
melatonin is a scavenger of oxyradicals and
peroxynitrite and exerts protective effects in
septic shock,
hemorrhagic shock and
inflammation. In the present study, we evaluated the effect of
melatonin treatment, in a model of
spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8
laminectomy. SCI in rats resulted in severe
trauma characterized by
edema, neutrophil infiltration and apoptosis (measured by
terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining). Infiltration of spinal cord tissue with neutrophils (measured as increase in
myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of
malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for
nitrotyrosine and
Poly(ADP-ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a)
spinal cord inflammation and tissue injury (histological score), (b)
nitrotyrosine and PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly reduced in spinal cord tissue obtained from rats treated with
melatonin (50 mg/kg i.
p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate set of experiment we have clearly demonstrated that
melatonin treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that treatment with
melatonin reduces the development of
inflammation and tissue injury events associated with
spinal cord trauma.