Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury.
Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Methylprednisolone (MP), by reducing edema and protecting the cell membrane against peroxidation, is the only pharmacological agent with a proven clinically beneficial effect on SCI. Melatonin, known as a free radical scavenger, has been shown to have an effect on lipid peroxidation following experimental SCI. The purpose of this study was to examine the effect of MP and melatonin on neurological, ultrastructural, and electrophysiological recovery. Female albino rats weighing 200-250 g were randomized into five groups of 18 rats each and six rats for the control group. Weight-drop trauma was performed for each group and a 30-mg/kg single dose of MP for rats in group 1, a 10-mg/kg single dose of melatonin for rats in group 2, and MP and melatonin in the same doses for rats in group 3 were administered immediately after trauma. The rats in group 4 were the vehicle group (treated with ethanol) and group 5 was the trauma group. The motor and somatosensory evoked potentials were recorded at the 4th hour, the 24th hour, and on the 10th day of the study for six rats in each group. Posttraumatic neurological recovery was recorded for 10 days using "motor function score" and inclined plane test. After electrophysiological study the rats were terminated for an analysis of lipid peroxidation level of the injured site of the spinal cord. Electron microscopic studies were performed to determine the effects of melatonin, MP, and the combined treatment with MP and melatonin on axons, neurons, myelin, nucleus, and intracytoplasmic edema. The groups treated with MP, melatonin, and a combination of both had significantly enhanced electrophysiological, biochemical, and neurological recovery and also showed better ultrastructural findings than the trauma and vehicle groups. Although combined treatment was significantly more effective on lipid peroxidation than melatonin or MP treatments alone, at the 10th day, neurobehavioral, electrophysiological, and ultrastructural recovery were at the same level. In conclusion, MP, melatonin, and MP and melatonin combined treatment modalities improved functional recovery at the same level. Future studies involving different doses of melatonin and different dose combinations with MP could promise better results since each drug has a different anti-oxidative mechanism of action.
Cayli
Suleyman R
SR
Department of Neurosurgery, Inönü University Medical Faculty, PK 230, Malatya, Turkey. srcayli@hotmail.com
Kocak
Ayhan
A
Yilmaz
Ugur
U
Tekiner
Ayhan
A
Erbil
Mine
M
Ozturk
Cetin
C
Batcioglu
Kadir
K
Yologlu
Saim
S
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; 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; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D008550:Melatonin; D008775:Methylprednisolone