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| YANG Liang,LV Decheng,ZHENG Lianjie.Effects and mechanism of FTY720 on neurofunctional recovery after acute spinal cord injury in rats[J].Chinese Journal of Spine and Spinal Cord,2012,(4):339-345. |
| Effects and mechanism of FTY720 on neurofunctional recovery after acute spinal cord injury in rats |
| Received:September 05, 2011 Revised:December 12, 2011 |
| English Keywords:Acute spinal cord injuries FTY720 Caspase-3 Apoptosis Rat |
| Fund:基金项目：辽宁省教育厅资助课题（编号：L2010105） |
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| English Abstract: |
| 【Abstract】 Objectives: To observe the effect of FTY720 on acute spinal cord injury (ASCI) and explore its possible mechanism. Methods： One hundred and sixty-eight pre-numbered Sprague-Dawley rats were randomly divided into three groups of 56 each as group A, B and C. In group A(sham operation group), rats were administered with 0.3ml saline by gavage after laminectomy but without contusion. In group B and group C, animal ASCI model was established by Allen′s WD method at the T9 level of spinal cord. After operation, rats in group B(control group) were also administered with saline at same dose, and rats in group C(treated group) were administered by gavage with 0.3ml FTY720-saline(3mg/kg body weight). For 8 rats of every group, functional recovery was evaluated after ASCI via inclined plane test and standardized Basso, Beattie and Bresnahan(BBB) locomotor scoring system at 1d, 3d, 7d, 14d, 21d. Rats of each group were sacrificed at 6h, 12h, 24h, 48h, 72h, 7d, 21d(n=8 per different time point) after spinal cord injury, and spinal cord tissues were collected and sections were made to do HE stain to observe the necrosis of injured spinal cord, infiltration of inflammatory cells, formation of glial scar and the size of syringomyelia cavities. Then, the numbers of lymphocytes(12h), inflammatory cells(12h、72h), scar cells(7d) and syringomyelia cavity size(21d) were calculated or measured. Sections of the time point at 6h, 12h, 24h, 48h, 72h were made to do SP immunohistochemical stain to observe expression of caspase-3 and Tunel stain to observe apoptosis of cells, then immunostain positive cells were calculated. All the data were statistically analyzed using SPSS 13.0 computer package. Results: The BBB scores and the results of inclined plane at the different time points in group B and C were both lower than those in group A(P<0.05), but no significant difference between group B and group C at 1d after spinal cord injury（P>0.05）, therefore functions of group C were better than group B at 3d, 7d, 14d, 21d (P<0.05). HE stain showed normal in group A at each time point; in group B and C, it showed bleeding and hematoma at 6h, gradual hydroncus, liquefaction necrosis combined with inflammatory cells infiltrating(neutrophil, lymphocyte, mononuclear cells mainly) at 12h to 48h, syringomyelia cavities forming surrounded by lots of inflammatory cells(gitter cells/mononuclear cells mainly) at 72h, the number of inflammatory cells in group B was significantly more than that in group C at 12h and 72h(P<0.05), the number of lymphocytes in group C was less than that in group B at 12h(P<0.05); at 7d, hydroncus decreased, glial scar formed around syringomyelia cavities, the glial scar density in group B was significantly higher than that in group C(P<0.05); at 21d, the syringomyelia cavities in group B were significantly larger than those in group C(P<0.05). Positive caspase-3 expression or neural apoptosis was not observed in group A at the different time points. The number of apoptotic cells increased with time increasing of acute spinal cord injury, peaked at 24 hours following injury, and then gradually reduced. However, neural apoptosis remained at a high level. Caspase-3 expression positively correlated with neural apoptosis. Caspase-3 expression and neural apoptosis in group C were significantly lower than those in group B(P<0.05). Conclusions: FTY720 can inhibit the expression of caspase-3 and the apoptosis of cells after ASCI and provide neuroprotective effects, so as to reduce secondary spinal cord injury and improve spinal nerve recovery. |
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