Metoprolol treatment decreases tissue myeloperoxidase activity after spinal cord injury in rats.
ABSTRACT Neutrophil infiltration has been reported to play an important role in spinal cord injury (SCI). In addition to their cardioprotective effects, beta-blockers have been found to have neuroprotective effects on the central nervous system, but their effect on SCI has not yet been studied. In the current study, we investigated the effect of metoprolol on myeloperoxidase (MPO) activity, a marker of neutrophil activation, in the spinal cord after experimental SCI in rats. Rats were divided into six groups: controls received only laminectomy and spinal cord samples were taken immediately; the sham operated group received laminectomy, and spinal cord samples were taken 4h after laminectomy; the trauma only group underwent a 50g/cm contusion injury but received no medication; and three other groups underwent trauma as for the trauma group, and received 30mg/kg methylprednisolone, 1mg/kg metoprolol, or 1mL saline, respectively. All the medications were given intraperitoneally as single doses, immediately after trauma. Spinal cord samples were taken 4h after trauma and studied for MPO activity. The results showed that tissue MPO activity increased after injury. Both metoprolol and methylprednisolone treatments decreased MPO activity, indicating a reduction in neutrophil infiltration in damaged tissue. The effect of metoprolol on MPO activity was found to be similar to methylprednisolone. In view of these data, we conclude that metoprolol may be effective in protecting rat spinal cord from secondary injury.
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ABSTRACT: After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI.Journal of Neuroscience Research 03/2011; 89(3):373-80. · 2.97 Impact Factor
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ABSTRACT: After acute spinal cord injury (SCI), a large number of axons are lost by a cascade of pathophysiological events known as a secondary injury. The main aim of the current study was to investigate the potential neuroprotective effects of curcumin on lipid peroxidation (LPO), neurological function, and ultrastructural findings after SCI. Forty adult Wistar albino rats were randomized into five groups: control, SCI alone (50 g/cm weight drop), methylprednisolone sodium succinate (MPSS) (30 mg/kg), curcumin + dimethyl sulfoxide (DMSO) (300 mg/kg), and DMSO alone (0.1 mg/kg). Administration of curcumin significantly decreased LPO in first 24 hours. However, there were no differences in the neurological scores of injured rats between the medication groups and the control group. Curcumin was more effective than DMSO and MPSS in reducing LPO, whereas DMSO was more effective than curcumin and MPSS in minimizing ultrastuctural changes. The results of this study indicate that curcumin exerts a beneficial effect by decreasing LPO and may reduce tissue damage. Since ultrastructural and neurological findings does not support biochemical finding, our findings do not exclude the possibility that curcumin has a protective effect on the spinal cord ultrastructure and neurological recovery after SCI. A combination of curcumin with other vehicle may also have a considerable synergy in protecting spinal cord.Turkish neurosurgery 01/2012; 22(2):189-95. · 0.58 Impact Factor