| The primary damage produced by spinal cord trauma is often limited, but it may be progressive to extensive tissue damage because of pathophysiological mechanisms that are activated following the primary injury. It is now wildly thought that the main secondary injury processes are involved in post-traumatic ischemia-reperfusion, glutamate excitotoxicity, Ca2+overload. apoptosis, inflammation, elaboration of oxygen free radicals and oxidative stress. Since the mechanisms involved are not completely clarified, the clinically pharmacological intervention is very difficulty. Although more investigations have been done in improving the neurological recovery of experimental animals subjected to spinal cord injury (SCI), the otucome are not satisfactory.Among the numerous pathophysiological mechanisms had been postulated to explain the secondary damage, oxygen free radical-induced lipid peroxidation is one of the most important factors participating in posttraumatic degeneration of the spinal cord. The results obtained from recent studies in preventing from tissue damage secondary to the traumatical brain injury and the heart or kidney ischemia, have showed that the elevated level of free iron capable to catalyze oxygen radical production and lipid peroxidation which result in tissue injury. Whether the free iron is involved in SCI and its effects on lipid peroxidation areunknown. On the other hand, application of iron chelating agents and some antioxidant in protecting brain, heart, kidney against the secondary injury appears to be effective, but still unknown against secondary spinal cord injury. Thus, the objectives of this project were to investigate the roles of free iron in the SCI through observation of changes of free iron and its relationship with lipid peroxidation, and to investigate the effective of different pharmacological intervention.Part I Changes of free iron and lipid peroxidation after SCI of rat spinal cordAll male SD rats were randomly divided into the following three groups: Group A received no operation; Group B received only laminectomy (sham); and Group C received both laminectomy and traumatic injury (SCI model). The SCI animal models were made by using an improved Allen's weight-drop device (50g-cm) on Ti2. Rats were sacrificed at 0.5, 1, 3, 6, 12, 24h after injury, the levels of free iron, lipid peroxidation and some antioxidant of injury spinal cord were respectively measured by biochemical technique. In group C, the level of free iron showed a significant increase at 0.5 h as compared to Group B or A, a return to the control level at 6h; the level of MDA increased at 0.5h, peaked at 3h, returned to the control level at 12h; the level of GSH and GSH-PX decreased under the control level at 12h, the activity of NOS reduced at 0.5 h, returned to the control at 6h. Free iron and lipid peroxidation concentration in injuried rats are significantly and positively correlated from 0.5 h to 3h. The results suggested that free iron may be associated with the SCI.Part II Effects of microinjacting free iron on the lipid peroxidation in spinal cordFerrous citrate(0.1?l,12nM)was intraspinally microinjected at T12in normal SD rats, and equal volume Ringer's solution was used in control group. The level of MDA was determined at the different periods of 12h, 24h, and 48h after miroinjection. Histological determination was done 3 days after miroinjection. There was a peak increase of level of MDA 12h after miroinjection, and a maintained higher level between 24 and 48h than the controls. The histological changes caused by iron injection were well consistent with the observation of the SCI model t>y weight-drop insult, with hemorrhage, destruction of tissue, degradation and necrosis of tissue cells. The results suggested that free iron may have a toxicity in the spinal cord tissues.Part III Effects of free iron on the changes of lipid peroxidation in spinal cord homogenateTo the homogenates of spinal cord, the Ringer's solution, ferrous citrate (10 ?M...
|
PDF Full Text Request