Dose-dependent neuroprotective effects of melatonin on experimental spinal cord injury in rats

Background: This report examines the dose-dependent effects of melatonin on early lipid peroxidation levels, ultrastructural changes, and neurological function in experimental spinal cord injury (SCI) by comparing them with therapeutic levels of methylprednisolone in rats. Methods: SCI was performed by an aneurysm clip placed extradurally at the level of T10. Rats were randomly divided into 6 groups of 10 rats each. Group 1 (sham) received only laminectomy; group 2 (control) received SCI; group 3 (placebo) received SCI and physiological saline; group 4 received methylprednisolone (30 mg/kg); groups 5 and 6 received melatonin at doses of 50 or 100 mg/kg, respectively, after SCI. Rats were neurologically tested 24 hours after trauma. Spinal cord samples were harvested for both lipid peroxidation levels and ultrastructural histopathological evaluation. Results: Neurological scores of rats were not different in SCI groups. Lipid peroxidation levels are significantly restricted only in methylprednisolone group at 24 hours. Melatonin-treated groups showed more ultrastructural improvement on electron microscopic studies when compared with methylprednisolone group. However, the therapeutic effects of melatonin were mainly observed on white matter of spinal cord in ultrastructural investigation. There was significant difference between metatonin dose groups increasing with dose. Conclusions: Results showed that melatonin has no significant dose-dependent effects on early lipid peroxidation but rather some neuroprotective effects on both axons and myelin sheaths of white matter in ultrastructural observations when compared with methylprednisolone. These effects significantly augmented with dose increase. (c) 2005 Elsevier Inc. All rights reserved.