Abstract
The clinical outcome of spinal cord injury (SCI) depends in part on the extent of secondary damage, to which apoptosis contributes. The CD95 and tumor necrosis factor (TNF) ligand/receptor systems play an essential role in various apoptotic mechanisms. To determine the involvement of these ligands in SCI-induced damage, we neutralized the activity of CD95 ligand (CD95L) and/or TNF in spinal cord-injured mice. Therapeutic neutralization of CD95L, but not of TNF, significantly decreased apoptotic cell death after SCI. Mice treated with CD95L-specific antibodies were capable of initiating active hind-limb movements several weeks after injury. The improvement in locomotor performance was mirrored by an increase in regenerating fibers and upregulation of growth-associated protein-43 (GAP-43). Thus, neutralization of CD95L promoted axonal regeneration and functional improvement in injured adult animals. This therapeutic strategy may constitute a potent future treatment for human spinal injury.
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Acknowledgements
This work was supported by the Christopher Reeve Paralysis Foundation. We thank A. Forde for critical reading of the manuscript.
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Demjen, D., Klussmann, S., Kleber, S. et al. Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury. Nat Med 10, 389–395 (2004). https://doi.org/10.1038/nm1007
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DOI: https://doi.org/10.1038/nm1007
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