The evaluation of the effects of the geranylgeranylacetone on the secondary injury of the spinal cord in experimental acute spinal cord injuries

ABSTRACTTHE EVALUATION OF THE EFFECTS OF THEGERANYLGERANYLACETONE ON THE SECONDARY INJURY OF THESPINAL CORD IN EXPERIMENTAL ACUTE SPINAL CORD INJURIESAs a result of traumatic spinal cord injury, damage in the cord is occured with the primary andsecondary mechanisms. Pimary injury is occured when the trauma is happened and is result fromcompression, contüsion, and laceration of the spinal cord. The degree of the primary injury isdepend on the strength of the cause, duration of the influence, and the energy amount which isabsorbed by the spinal cord. The pathological process in the primary injury is believed to beirreversible.Secondary injury is a pathological process which happens a few minutes after primary injury andit continues throughout a few weeks. A most important factor in the formation of the secondaryinjury is the insufficiency of the energy. The cause of this is ischemia resulted from the damagedperfusion. To get under control the ischemia which is resulted from the damaged perfusion isbelieved to be important in the limitation of the secondary injury.Until today, several experimental studies hve been performed to understand thephysiopathological mechanisms and the treatment modalities in the traumatic spinal cord injuries. In1978, Rivlin and Tator created ischemia by the way of mechanical truma plus vascular influence inthe clip compression model. It has been seen that it is similar to the spinal cord injury followed bytrauma (2,16).Until 1980, free oxygen radicals, calcium, opioid receptörs, and lipid peroxidations have beenthought to be responsible for the secondary injury, and the studies have been performed in thisdirection (6,33). In nowadays, apoptosis, intracellular protein synthesis, ang glutaminergicmechanisms are been thought to be responsible for secondary injury (33). As a result of experimentalstudies, it has been seen that GGA augments the release of the HSP 70 and have cytoprotectiveeffects on liver, retina, brain, bowel, and stomach cells (41).The augmentation of the release of the HSP 70 triggers the proteins which are responsible inthe antiapoptotic mechanism. İt has been shown that it decreases the level of TNF-alpha whichincreases the inflammatory cells in the lesion site and responsible for the apoptotic mechanism. İthas been shown that the augmentation of the myeloperoxidaz (MPO) in the lesion site increases theactivity of the inflammatory cells. İt has been thouhgt that HSP 70, decreaese the inflammatoryresponse in the lesion site and have cell protective effect (40,41).In this study, we examined the effects of the GGA which has a nöroprotective effect which hasbeen shown by studies in the acute experimental spinal cord injury on the secondary injury. Weshowed that GGA decreases the ischemia and necrosis area when it adminestered 2 hours beforeperforming spinal cord injury. Whereas 2 hours after performing spinal cord injury, we didn?t see thatGGA has significiant effect on the ischemia and necrosis area. Similarly, increase in the release ofthe HSP 70 was found in the group whis was GGA adminestered 2 hours before. In the group in whichGGA adminestered 2 hours after we didn?t see significiant increase. When the TNF-alpha levelsevaluated, in the grorup in which GGA adminestered 2 hours before we saw significiant degree ofdecrease. In the group in which GGA adminestered 2 hours after we didn?see significiant degree ofdecrease.The changes in the levels of MPO didn?t find statistically signiciant. GGA have been believed tohave cytoprotective effect in both our study and studies which had been performed before.Whereas by the which the mechansim it affects still unknown. Studies which had been performedhas shown that it affects by increasing the HSP 70 release.