Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord
Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord
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DOI：
10.1111/j.1460-9568.2007.05859.x
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发表时间：
2007-11-01
影响因子：
3.4
通讯作者：
Bolsover, Stephen
中科院分区：
文献类型：
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作者：
Fabes, Jez;Anderson, Patrick;Bolsover, Stephen
脊髓损伤常常导致永久性的功能丧失，因为长轴突不能在中枢神经系统中再生。Eph受体通过对肌动蛋白细胞骨架的作用抑制轴突的延伸。我们以前曾报道，损伤后EphA4出现在皮质脊髓轴突残端的高水平，而同源配体ephrinB2，在病变部位上调，以限制受伤的轴突。在这项研究中，我们已经注入损伤的脊髓与EphA4的肽拮抗剂。在治疗的动物中，不存在皮质脊髓束损伤后通常出现的退行性变性。相反，皮质脊髓束轴突发芽并进入病变中心。在皮质脊髓束功能的行为测试中，肽治疗相对于对照显著改善了恢复。这些结果表明，阻断EphA4可能有助于未来成功的脊髓损伤临床治疗。
Spinal cord injury often leads to permanent incapacity because long axons cannot regenerate in the CNS. Eph receptors inhibit axon extension through an effect on the actin cytoskeleton. We have previously reported that after injury EphA4 appears at high levels in stumps of corticospinal axons, while a cognate ligand, ephrinB2, is upregulated at the lesion site so as to confine the injured axons. In this study we have infused lesioned spinal cords with a peptide antagonist of EphA4. In treated animals the retrograde degeneration that normally follows corticospinal tract injury is absent. Rather, corticospinal tract axons sprout up to and into the lesion centre. In a behavioural test of corticospinal tract function, peptide treatment substantially improved recovery relative to controls. These results suggest that blocking EphA4 is likely to contribute to a future successful clinical treatment for spinal cord injury.