Hill Caitlin E
Burke Medical Research Institute, White Plains, NY, United States; Weill Cornell Medicine, Feil Family Brain and Mind Research Institute, New York, NY, United States.
Neurosci Lett. 2017 Jun 23;652:11-24. doi: 10.1016/j.neulet.2016.11.002. Epub 2016 Nov 5.
Following spinal cord injury (SCI), most axons fail to regenerate and instead form large, swollen endings generically called 'retraction bulbs.' These endings form and persist after SCI even under experimental therapeutic conditions where significant CNS regeneration occurs. Although retraction bulbs can arise from either activation of degenerative processes or deficits in regenerative processes, they are typically grouped as a single type of axonal ending. To facilitate the targeting of axonal endings for SCI repair, this review focuses on dissecting the different types of axonal endings present following injury by examining them in the context of the temporal, degenerative and regenerative changes that occur following injury. The stages of axonal dieback (also known as axonal retraction) and the steps necessary for successful axonal regeneration are outlined. The types of axonal endings that can arise as an axon successfully or unsuccessfully mounts a regenerative response are examined, with an emphasis on retraction bulbs, growth cones, and collapsed growth cones. Retraction bulbs are subdivided into those that arise from a failure to form a growth cone (endbulbs) and those that stall in response to inhibitory gradients (dystrophic axonal endings). The current understanding of the mechanisms that lead to the development of different types of axonal endings, how different experimental therapeutic interventions may act on different types of axonal endings, the current gaps in understanding the sites of action of some pro-regenerative therapies, and some of the methodological challenges to studying different types of axonal endings are discussed.
脊髓损伤（SCI）后，大多数轴突无法再生，而是形成通常称为“回缩球”的大而肿胀的末端。即使在发生显著中枢神经系统再生的实验性治疗条件下，这些末端在脊髓损伤后仍会形成并持续存在。尽管回缩球可能源于退化过程的激活或再生过程的缺陷，但它们通常被归为单一类型的轴突末端。为了便于针对脊髓损伤修复靶向轴突末端，本综述着重通过在损伤后发生的时间、退化和再生变化的背景下对其进行检查，来剖析损伤后存在的不同类型的轴突末端。概述了轴突回缩（也称为轴突退缩）的阶段以及成功轴突再生所需的步骤。研究了轴突在成功或未成功进行再生反应时可能出现的轴突末端类型，重点是回缩球、生长锥和塌陷生长锥。回缩球可细分为因未能形成生长锥而产生的（终球）和因对抑制性梯度作出反应而停滞的（营养不良性轴突末端）。讨论了目前对导致不同类型轴突末端形成的机制的理解、不同实验性治疗干预可能如何作用于不同类型的轴突末端、目前在理解一些促再生疗法的作用位点方面存在的差距以及研究不同类型轴突末端面临的一些方法学挑战。
