One hundred years ago, Ramón y Cajal, considered by many as the founder of modern neuroscience, stated that neurons of the adult central nervous system (CNS) are incapable of regenerating. Yet, recent years have seen a tremendous expansion of knowledge in the molecular control of axon regeneration after CNS injury. We now understand that regeneration in the adult CNS is limited by (1) a failure to form cellular or molecular substrates for axon attachment and elongation through the lesion site; (2) environmental factors, including inhibitors of axon growth associated with myelin and the extracellular matrix; (3) astrocyte responses, which can both limit and support axon growth; and (4) intraneuronal mechanisms controlling the establishment of an active cellular growth programme. We discuss these topics together with newly emerging hypotheses, including the surprising finding from transcriptomic analyses of the corticospinal system in mice that neurons revert to an embryonic state after spinal cord injury, which can be sustained to promote regeneration with neural stem cell transplantation. These gains in knowledge are steadily advancing efforts to develop effective treatment strategies for spinal cord injury in humans.

一百年前，被许多人视为现代神经科学奠基人的 Ramón y Cajal 指出，成人中枢神经系统 (CNS) 的神经元无法再生。然而，近年来，中枢神经系统损伤后轴突再生的分子控制方面的知识有了巨大的扩展。我们现在了解到，成人中枢神经系统的再生受到以下因素的限制：（1）无法形成轴突附着和通过损伤部位伸长的细胞或分子底物；(2) 环境因素，包括与髓磷脂和细胞外基质相关的轴突生长抑制剂；(3) 星形胶质细胞反应，既可以限制也可以支持轴突生长；(4) 控制活跃细胞生长程序建立的神经元内机制。我们与新出现的假设一起讨论这些主题，包括对小鼠皮质脊髓系统的转录组学分析的惊人发现，即神经元在脊髓损伤后恢复到胚胎状态，这可以持续促进神经干细胞移植的再生。这些知识的增长正在稳步推进开发有效的人类脊髓损伤治疗策略的努力。