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 methylprednisone in rats.


METHODS
SCI was performed by an aneurysm clip placed extradurally at the level of T10. Rats were randomly divided into six 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 methylprednisone (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 methylprednisone group at 24 hours. Melatonin-treated groups showed more ultrastructural improvement on electron microscope studies when compared with methylprednisone group. However, the therapeutic effects of melatonin were mainly observed on white matter of spinal cord in ultrastructural investigation. There was significant difference between melatonin dose groups increasing with dose.


CONCLUSIONS
Results showed that melatonin has no significant dose-dependent effects on early lipid peroxidation bur rather some neuroprotective effects on both axons and myelin sheaths of white matter in ultrastructural observations when compared with methylprednisone. These effects significantly augmented with dose increase.
Gül
Sanser
S
Department of Neurosurgery, Karaelmas University, Medical Faculty, Zonguldak 67100, Turkey.
Celik
Suat Erol
SE
Kalayci
Murat
M
Taşyürekli
Mustafa
M
Cokar
Necla
N
Bilge
Turgay
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D008775:Methylprednisolone / Q000494:pharmacology / Q000627:therapeutic use; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D008550:Melatonin; D008775:Methylprednisolone