Abstract
Nitric oxide (NO) may aggravate neuronal injury after spinal cord injury (SCI). We hypothesized that NO produced by inducible nitric oxide (iNOS) accelerates secondary damage to spinal tissue, which may be reversed by a neuroprotectant, melatonin. This study investigated the effects of combination therapy with melatonin (10mg/kg) and exercise (10m/min) on the recovery of SCI caused by contusion. We examined locomotor recovery, iNOS gene expression as well as autophagic, apoptotic signaling, including Beclin‐1, LC3, p53, IKK¥á protein expression, and histological alterations of ventral horn. Melatonin‐treated exercise resulted in a significant increased hindlimb movement (P<.05), decreased level of iNOS mRNA (P<.05), and increased motor neurons in ventral horn than control SCI and exercised SCI, together with no effect of other screened signaling molecules. This study shows that the combination 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 neural fatigue and impairment. Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea.
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