Assessment of therapeutic and preservative effects of cyclosporine in experimental rat spinal injury model

Introduction: Spinal cord injuries still conserve their importance due to their serious socio-economic problematical results; and no consensual treatment algorythm has yet been concluded. They are assessed under two subtitles as primary and secondary injuries. Primary injury includes compressions, contusions and lacerations which have emerged during the trauma. The amount of damage at this stage is correlated to the magnitude, duration and the impact of energy absorbed. On the other hand, secondary injury is a process ( which is ) composed of metabolic and biochemical facts that arise during the very first minutes, those were triggered by the primary injury, and lasts for days after. Majority of the clinical and experimental trials about this issue is aimed at preventing the secondary injury. Method: In this trial preservative and therapeutic effects of cyclosporine A in secondary injury condition; were studied -by the help of histopathological (Luxol fast blue, hematoxilene-eosinophil and TUNEL dying method) and damage scoring physical examination (inclined plane, motor examination) methods- over the spinal injury model, which was created with clip compression procedure. 18 Sprague Dawley breed mature female rats were exploited in this study. Following the anaesthesia, with a skin incision through the space between T7-T9 (thoracal vertebras), paravertebral muscles were dissected; and three groups, 6 rats in each, were comprised: group 1 (the control group), group 2 (laminectomy + cord compression) and group 3 (laminectomy + cord compression + cyclosporine-A). Subjects were observed for 10 days and neurophysiological functions were recorded on days 1, 3, 5 and 10. All were sacrificed at day 10 for the histopathological examination. Findings: In histopathological examination, it was shown that the trial group (which was) exposed to Cyclosporine-A (Sandimmune-Novartis IV vial) had a less area of damage -in diameters-, fewer number of degenerated white matter axons, apoptotic cells and necrosis; and in contrast to the trauma group, the structural unity was preserved better whereas the trauma group had a wide edema on the injury site with an increase in the inflammatory cells and vacuolized axonal structures in the white matter. Mann Whitney-U statistical analysis showed a significant diminution at group 3 in comparison to group 2 regarding apoptosis and necrosis (p<0.05). With Kruskal Wallis test, a significant statistical difference between all groups, in terms of motor function scores and inclined plane results, was seen; and this difference got prominence for inclined plane in day 10 (p:0.001; p<0.05), in 5th and 10th days fort he motor function scores (p:0.00; p<0.01). When two groups were compared with Mann-Whitney U test, there was a distinction after day 5, in inclined plane, and this difference reached a statistical significance at the 10th day (p:0.012; p<0.05). Values of motor function scores presented a significant difference by day 5 and at last the significance became bigger on day 10 (p:0.002; p<0.001). Results: In our study of experimental, rat spinal injury model; we are convinced that we are able to present both the preservative [neuroprotective, (necrosis/apoptosis datas are in favour of the group received Cyclosporine-A)] and therapeutic effects [regenerative, (inclined plane and motor function score datum are in favour of the group received Cyclosporine-A)] of Cyclosporine-A on the secondary spinal injury, which is statistically significant. Key words: Laminectomy, rat, spinal compression, cyclosporine A, trauma