The role of Fas-mediated apoptosis after traumatic spinal cord injury

Study Design. Functional recovery and histopathological change after spinal cord injury in the Fas-deficient mice and the wild-type mice were investigated. Objectives. To investigate the role of the Fas/Fas ligand ( FasL) system as a signal transduction pathway leading to apoptosis after spinal cord injury. Summary of Background Date. Apoptosis observed after spinal cord injury has recently gained widespread interest as a cause of collateral damage after the initial injury. Apoptosis mediated by the Fas antigen in the post-ischemic brain or spinal cord was reported. Recently, the upregulation of Fas after spinal cord injury was also reported. However, the influence of Fas-mediated apoptosis on the extent of the secondary spinal cord injury has not yet been clarified. Methods. We investigated Fas-mediated apoptosis after spinal cord injury and examined the behavioral changes and the histopathological changes after spinal cord injury using MRL/Mp-lpr/lpr (MRL/lpr) mice, which were Fas-deficient mutant mice, and MRL/Mp-+/+ (MRL/+) mice, which were Fas-positive wild-type mice. Results. Locomotor recovery after spinal cord injury in MRL/lpr mice was superior to that observed in MRL/+ mice. In addition, the damaged area in MRL/lpr mice was significantly smaller than that seen in MRL/+ mice. Further, the frequency of apoptotic cells in the injured spinal cord of MRL/lpr mice was significantly less than that in MRL/+ mice. Conclusion. We demonstrated the appearance of Fas-mediated apoptosis in the spinal cord after spinal cord injury. In addition, we elucidated for the first time that Fas-mediated apoptosis following spinal cord injury played an important role in the spinal cord damage and the ultimate neurologic injury.