Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury
Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury
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DOI：
10.1038/nm1007
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发表时间：
2004-04-01
期刊：
影响因子：
82.9
通讯作者：
Martin-Villalba, A
中科院分区：
文献类型：
--
作者：
Demjen, D;Klussmann, S;Martin-Villalba, A
脊髓损伤（SCI）的临床结果部分取决于继发性损伤的程度，细胞凋亡有助于继发性损伤。CD 95和肿瘤坏死因子（TNF）配体/受体系统在各种凋亡机制中起重要作用。为了确定这些配体参与SCI诱导的损伤，我们中和了脊髓损伤小鼠中CD 95配体（CD 95 L）和/或TNF的活性。治疗性中和CD 95 L（而非TNF）可显着减少SCI后的细胞凋亡死亡。用CD 95 L特异性抗体治疗的小鼠能够在损伤后数周开始主动后肢运动。运动性能的改善反映在再生纤维的增加和生长相关蛋白-43（GAP-43）的上调。因此，CD 95 L的中和促进了损伤的成年动物的轴突再生和功能改善。这种治疗策略可能成为未来人类脊髓损伤的有效治疗方法。
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.