Nature Medicine10, 389 - 395 (2004)
Published online: 7 March 2004; | doi:10.1038/nm1007
Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury
Deana Demjen1, Stefan Klussmann1, Susanne Kleber1, Cecilia Zuliani1, Bram Stieltjes2, Corinna Metzger1, Ulrich A Hirt3, Henning Walczak3, Werner Falk4, Marco Essig2, Lutz Edler5, Peter H Krammer1
& Ana Martin-Villalba1
1
Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany.
2
Department of Radiology, German Cancer Research Center, 69120 Heidelberg, Germany.
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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