Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury

Abstract

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 antioxidative mechanism of action.

Antioxidant effects of curcumin in spinal cord injury in rats

“…Secondary injury after the primary impact includes different pathophysiological and biochemical events. [3][4][5][6][7][8][9][10][11][12][13] Oxygen-derived free radicals have been implicated in the pathogenesis of spinal cord neuronal injury after trauma. Decreasing the level of oxidative stress minimizes the secondary destruction effect after traumatic injury.…”

Alleviation of spinal cord injury by Ginkgolide B via the inhibition of STAT1 expression

“…Some studies have tried to manipulate the composition of inflammatory cells in mouse models of SCI but did not obtain satisfactory results (Shi et al, 2010;Lukáš et al, 2011), suggesting the necessity for the development of alternative treatments for secondary SCI. The JAK/STAT signaling pathway is activated immediately after SCI and is accompanied with morphological changes and cell apoptosis (Cayli et al, 2004). Other studies described the activation of STAT1 in cerebral focal ischemia and brain damage and many potent antioxidants exert their protective functions via inhibition of STAT1 phosphorylation and nuclear translocation (Choi et al, 2011;Xu et al, 2011;Rong et al, 2012).…”

Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury

“…EPO mediates tissue protection via multiple, interacting pathways (reviewed by Ghezzi and Brines in ref. 20), including a reduction of both apoptotic cell death and the reactive increases in proinflammatory cytokines (21), mobilization of endothelial progenitor cells, promotion of angiogenesis (22) and healing (23), restoration of vascular autoregulation (24)(25)(26), and reduction of lipid peroxidation (19).…”