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

Abstract

Functional recovery and histopathological change after spinal cord injury in the Fas-deficient mice and the wild-type mice were investigated. To investigate the role of the Fas/Fas ligand (FasL) system as a signal transduction pathway leading to apoptosis after spinal cord injury. [corrected] 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 postischemic 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. 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. 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. 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.