Synergistic effect of melatonin on exercise-induced neuronal reconstruction and functional recovery in a spinal cord injury animal model

Nitric oxide (NO) may aggravate neuronal damage after spinal cord injury (SCI). We hypothesized that NO produced by inducible nitric oxide synthase (iNOS) accelerates secondary damage to spinal tissue, which may be reversed by the neuroprotectant, melatonin. This study investigated the effects of combination therapy with melatonin (10 mg/kg) and exercise (10 m/min) on recovery from SCI caused by contusion. We examined locomotor recovery, iNOS gene expression, autophagic and apoptotic signaling, including Beclin-1, LC3, p53 and IKK alpha protein expression and histological alterations in the ventral horn of the spinal cord. Melatonin in combination with exercise resulted in significantly increased hindlimb movement (P < 0.05), a reduced level of iNOS mRNA (P < 0.05) and more motor neurons in the ventral horn, versus control SCI and SCI plus exercise alone, with no effect on the other signaling molecules examined. This study shows that combined therapy with melatonin and exercise reduces the degree of secondary damage associated with SCI in rats and supports the possible use of melatonin in combination with exercise to reduce the side effects related to exercise-induced fatigue and impairment.