| PrefaceTraumatic injury to the spine cord results in tissue necrosis and loss of function, and some axons are directly damaged by the physical deformation of the spinal cord (primary injury). However, it is likely that a large number of axons are lost due to a casade of pathochemical and/or pathosiological events ( secondary injury) that are initiated by the original insult. It is this secondary injury that would appear to be susceptible to pharmacological intervention. To explain this delayed tissue damage, numerous pathophysiological mechanisms have been postulated. It has been suggested that one of the most important factors precipitating posttraumatic degeneration in the spinal cord is oxygen free radical - induces lip-id peroxidation.Methyiprednisolone has been used extensively as a pharmacological tool in the treatment of experimental trautic soinal cord injury ( SCI). In clinical trials, methyiprednisolone has been shown to be an effective agent for the treatment of acute SCI. Numerous investigators is the ihibition of lipid peroxidation rather than glucocorticoid receptor activation. When administered in large doses,methyiprednisolone has been shown to be a powerful antioxidant.The pinel hormone melatonin is also a very potent free radical scavenger that has likewise been shown to enter the cell and nucleus. However, me thypred-nisolone possesses its neuroprotective effect by a direct membrane action. In previous studies, melatonin has been shown to protect against nucleic acid damage via an action involving generation of oxygen - based free radicals produced by the administration of chemical carcinogen safrole and ionizing raiation. Althoughmany studies have been published in ehich the effectiveness of metylprednisolone has been proven, such a therapeutic benefit for melatonin in SCI has not been previously demonstrated. In the present study, ew examined the possible potential protective effect of melatonin in experimental acute SCI. We compared the effects of melatonin with methylprednisolone, which has been suggested to protect the spinal cord from secondary injury from traumatized spinal cord tissue.Materials and MethodsMale Wistar rats weighing 230 to 280 g were used for the study. The rats, housed one in a cage, were given free access to food and water. The rats were pinned in the prone position. Following T5 - 12 midline skin incision, spinous processes and laminar arcs of T8 — 10 were removed with the assistance of a surgical microscope after paravertebral muscle dissection. Trauma was produced by the method described by Allen in 1911. The animals were subjected to 50 - g/ cm impact to the dorsal surface of the spinal cord, rendering them severly wounded and paraplegic. The force war applied via a stainless steel rod that was rounded at the surface, which made contact with the spinal cord after being dropped vertically through a calibrated tube. The injury apparatus was a 10 - cm guide tube that was positioned perpendicular to the center of the spinal cord.The rats were randomly allocated into four groups;trauma group of 18 rats in which, following surgical and traumatic interventions, 1 - cm injured spinal cord samples were removed at 2,24,72 hours posttrauma;methylprednisolone group of 18 animals in which a 30 - mg/kg single dose of methylprednisolone was administered through tail - vein 10 minutes after trauma, and 1 - cm samples of injured spinal cord were removed at 2, 24,72 hours posttrauma;melatonin group of 18 rats in which a 100 -mg/kg single dose of melatonin was given through tail - vein 10 minutes after trauma, and 1 - cm samples of injured spinal cord were removed at 2, 24, 72 hours posttrauma. Vehicle - treated group of 18 animals in which a same single dose of vehicle was administered through tail -vein 10 minutes after trauma, and 1 - cm samples of injured spinal cord were removed at 2, 24 , 72 hours posttrauma;Samples obtained from all groups were used for further study, such as iN-OS. Statistical significance between experiment groups was defined by using SPSS analysis.ResultsThe difference between methylprednisolone - treated group and trauma group was statistically significant (P =0. 019, 0. 004 and 0. 009 for samples obtained at 2, 24, and 72 hours postinjury, respectively). The difference between melatonin -treated group and trauma group was statistically significant (P =0. 016, 0.016 and 0.004 for samples obtained at 2, 24 and 72 hours postinjury, respectively). But the difference between melatonin - and methylprednisolone - treated groups was not statistically significant ( P =0. 927, 0. 520 and 0. 712 for samples obtained at 2, 234 and 72 hours postinjury, respectively). The difference between vehicle - treated group and trauma group was not statistically significant (P =0. 889, 0. 828 and 0. 711 for samples obtained at 2, 24, 72 hours postinjury, respectively ) .DiscussionTraumatic injury to the spinal cord results in tissue necrosis and loss of function, include primary injury and secondary injury. It is this secondary injury that would applear to be susceptible to pharmacological intervention, such as iN-OS.Methllprednisolone has been used extensively as a pharmacological tool in the treatment of experimental traumatic SCI. In clinical trails, methylprednisolone has been shown to be an effective agent for the treatment of acuted SCI. Numerous investigators have postulated that the neuroprotctive mechanism of action of steroids is the inhibition of lipid peroxidation rather than glucocorticoid recpe-tor activation. When administered in large doses, methyprednisolone has been shown to be a powerful antioxidant.Melatonin, N - acetil - 5 - methoxytriptamine, is a hormonal product ofpineal gland. Until recently it was generally thought that melatonin's receptors on cells. Certainly, the interactions of melatonin with these membrane - bound re-cptors are believed to mediate the endocrinological function and the circadian rhythm of melatonin. It has been recently discovered that melatonin is a very potent free radical scavenger as well as an electron donor. Thus, potentially, the indolamine not only protects biomolecules from free radical damage, but it may also repair electron - deficient biomolectiles by donating an electron to them. Melatonin "s efficacy as a free radical scavenger has been compared with mannitol and glutathione, the most effective exogenous and endogenous hydroxyl radical ( * OH) scavenger. The free radical quenching activity of melatonin does not require a receptor, and it enters all cells and passes all morphophysiological barriers. It is nontoxic, it is both lipophylic and hydrophilic, is rapidly absorbed, easy to produce, and it is inexpensive. Melatonins extreme diffusability is important for its scavenging action because this feature allows ti to enter all cells and every subcelluar compartent. It has also been shown that it may be bound in the nucleus, thereby providing on -side protection to DNA.Because of this antioxidant effect, methylprednisolone has been shown to be very effective in protecting the spinal cord from secondary injury and, when administered to animals or humans in antioxidant doses, improves chronic neurological recovery after SCI. This activity of methylprednisolone is independent of the steroid"s glucocorticoid receptor mediated activity. Unlike melatonin, it is known that the neuroprotective effect of methylprednisolone is by a direct membrane action.Interperitoneal administration of methylprednisolone and melatonin was shown to decrease remarkably levels of lipid peroxide at all time periods. Al-thought melatonin was shown to decrease lipid peroxidation in the 2" hour more than methylprednisolone, this difference was not statistically significant. This difference between trauma group and vehicle - treated group was not statistically significant.ConclusionsIn summary, data obtained from the present study confirm the therapeutic benefit of both melatonin and methylprednisolone. Melatonin provides protection of spinal cord against lipid peroxidation, which occurs as as result of trauma, and this protection at a given dose is not different from that provided by methylprednisolone. Melatonin may also possess some other unknows mechanisms that protect the spinal cord from secondary injury.In view of this numerous advantages and benefits, it may be the time to consider the use of melatonin in animal studies and clinical trails in patients with SCI.
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