Shriners Hospitals Pediatric Research Center and Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Exp Neurol. 2022 Nov;357:114198. doi: 10.1016/j.expneurol.2022.114198. Epub 2022 Aug 6.
Spinal cord injury (SCI) is a disastrous event causing irreversible loss of both sensory and motor function. After SCI, both ascending dorsal column axons and descending corticospinal tract (CST) axons undergo rapid degeneration that is subsequently followed by slow axonal dieback and retraction bulb formation. Pre-clinical studies over the last two decades using genetic and, to a lesser extent, pharmacological approaches have identified several molecules that regulate intrinsic axon regeneration after SCI. However, accumulating evidence suggests that the efficacy of intrinsic pro-regenerative molecules to enhance axon regeneration is considerably different between ascending dorsal column and descending CST axons following SCI. Here I describe the different molecules targeting intrinsic regeneration and their efficacy in triggering dorsal column and CST axon regeneration after SCI. First, I will briefly describe the general anatomy of dorsal column and CST axons as well as their acute and chronic response after SCI. Then, I will review the latest genetic and pharmacological studies identifying molecules targeting intrinsic axon regeneration and the efficacy of such molecules in promoting dorsal column and CST axon regeneration after SCI. Next, I will review accumulating evidence suggesting important differences in regenerative response between dorsal column and CST axons upon targeting intrinsic pro-regenerative molecules. Finally, I will suggest future research directions to uncover the downstream molecular mechanisms responsible for differences in regenerative response between dorsal column and CST axons following SCI.
脊髓损伤（SCI）是一种灾难性事件，会导致感觉和运动功能的不可逆转丧失。SCI 后，上行的背柱轴突和下行的皮质脊髓束（CST）轴突都经历快速退化，随后是缓慢的轴突死亡和回缩球形成。在过去的二十年中，通过使用遗传和在较小程度上使用药理学方法的临床前研究已经确定了几种调节 SCI 后内在轴突再生的分子。然而，越来越多的证据表明，内在促再生分子在增强 SCI 后上行背柱和下行 CST 轴突的轴突再生方面的功效在很大程度上不同。在这里，我将描述针对内在再生的不同分子及其在触发 SCI 后背柱和 CST 轴突再生方面的功效。首先，我将简要描述背柱和 CST 轴突的一般解剖结构以及它们在 SCI 后的急性和慢性反应。然后，我将回顾最新的遗传和药理学研究，确定针对内在轴突再生的分子以及这些分子在促进 SCI 后背柱和 CST 轴突再生方面的功效。接下来，我将回顾积累的证据，这些证据表明，在针对内在促再生分子时，背柱和 CST 轴突的再生反应存在重要差异。最后，我将提出未来的研究方向，以揭示 SCI 后背柱和 CST 轴突再生反应差异的下游分子机制。
