After an injury to the central nervous system (CNS), functional recovery is limited by the inability of severed axons to regenerate and form functional connections with appropriate target neurons beyond the injury. Despite tremendous advances in our understanding of the mechanisms of axon growth, and of the inhibitory factors in the injured CNS that prevent it, disappointingly little progress has been made in restoring function to human patients with CNS injuries, such as spinal cord injury (SCI), through regenerative therapies. Clearly, the large number of overlapping neuron-intrinsic and -extrinsic growth-inhibitory factors attenuates the benefit of neutralizing any one target. More daunting is the distances human axons would have to regenerate to reach some threshold number of target neurons, e.g., those that occupy one complete spinal segment, compared to the distances required in most experimental models, such as mice and rats. However, the difficulties inherent in studying mechanisms of axon regeneration in the mature CNS in vivo have caused researchers to rely heavily on extrapolation from studies of axon regeneration in peripheral nerve, or of growth cone-mediated axon development in vitro and in vivo. Unfortunately, evidence from several animal models, including the transected lamprey spinal cord, has suggested important differences between regeneration of mature CNS axons and growth of axons in peripheral nerve, or during embryonic development. Specifically, long-distance regeneration of severed axons may not involve the actin-myosin molecular motors that guide embryonic growth cones in developing axons. Rather, non-growth cone-mediated axon elongation may be required to propel injured axons in the mature CNS. If so, it may be necessary to use other experimental models to promote regeneration that is sufficient to contact a critical number of target neurons distal to a CNS lesion. This review examines the cytoskeletal underpinnings of axon growth, focusing on the elongating axon tip, to gain insights into how CNS axons respond to injury, and how this might affect the development of regenerative therapies for SCI and other CNS injuries.

在中枢神经系统（CNS）受伤后，功能性恢复受到切断的轴突无法再生并无法与损伤后适当的目标神经元形成功能连接的限制。尽管我们对轴突生长的机制以及受伤害的中枢神经系统的抑制因子的理解有了巨大的进步，但令人失望的是，在恢复中枢神经系统损伤的人类患者（如脊髓损伤）的功能方面，令人失望的进展很小，通过再生疗法。显然，大量重叠的神经元内在和外在生长抑制因子减弱了中和任何一个靶标的益处。更令人生畏的是人类轴突必须再生的距离才能达到一定数量的目标神经元，例如占据一个完整脊柱节段的目标神经元，与大多数实验模型（例如小鼠和大鼠）所需的距离进行比较。然而，研究成熟的中枢神经系统轴突再生机制固有的困难体内 已导致研究人员严重依赖于周围神经轴突再生或生长锥介导的轴突发育研究的推断 体外 和 体内。不幸的是，来自包括横断的七lamp鳗脊髓在内的几种动物模型的证据表明，成熟的中枢神经系统轴突的再生与周围神经中轴突的生长或胚胎发育过程之间存在重要差异。具体而言，切断的轴突的远距离再生可能不涉及在发育中的轴突中引导胚胎生长锥的肌动蛋白-肌球蛋白分子马达。而是，可能需要非生长锥介导的轴突伸长来推动成熟的中枢神经系统中受伤的轴突。如果是这样，可能有必要使用其他实验模型来促进再生，该再生足以接触中枢神经系统病变远端的关键数目的目标神经元。这篇评论研究了轴突生长的细胞骨架基础，重点是轴突尖端的延长，以深入了解中枢神经系统轴突对损伤的反应，