Katoh Hiroyuki, Yokota Kazuya, Fehlings Michael G
Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada.
Department of Orthopaedic Surgery - Surgical Sciences, School of Medicine, Tokai University, Tokyo, Japan.
Front Cell Neurosci. 2019 Jun 6;13:248. doi: 10.3389/fncel.2019.00248. eCollection 2019.
Significant progress has been made in the treatment of spinal cord injury (SCI). Advances in post-trauma management and intensive rehabilitation have significantly improved the prognosis of SCI and converted what was once an "ailment not to be treated" into a survivable injury, but the cold hard fact is that we still do not have a validated method to improve the paralysis of SCI. The irreversible functional impairment of the injured spinal cord is caused by the disruption of neuronal transduction across the injury lesion, which is brought about by demyelination, axonal degeneration, and loss of synapses. Furthermore, refractory substrates generated in the injured spinal cord inhibit spontaneous recovery. The discovery of the regenerative capability of central nervous system neurons in the proper environment and the verification of neural stem cells in the spinal cord once incited hope that a cure for SCI was on the horizon. That hope was gradually replaced with mounting frustration when neuroprotective drugs, cell transplantation, and strategies to enhance remyelination, axonal regeneration, and neuronal plasticity demonstrated significant improvement in animal models of SCI but did not translate into a cure in human patients. However, recent advances in SCI research have greatly increased our understanding of the fundamental processes underlying SCI and fostered increasing optimism that these multiple treatment strategies are finally coming together to bring about a new era in which we will be able to propose encouraging therapies that will lead to appreciable improvements in SCI patients. In this review, we outline the pathophysiology of SCI that makes the spinal cord refractory to regeneration and discuss the research that has been done with cell replacement and biomaterial implantation strategies, both by itself and as a combined treatment. We will focus on the capacity of these strategies to facilitate the regeneration of neural connectivity necessary to achieve meaningful functional recovery after SCI.
脊髓损伤（SCI）的治疗已取得显著进展。创伤后管理和强化康复方面的进步显著改善了SCI的预后，将曾经的“不治之症”转变为可存活的损伤，但残酷的现实是，我们仍然没有一种经过验证的方法来改善SCI导致的瘫痪。脊髓损伤后神经元传导跨损伤病灶的中断会导致损伤脊髓出现不可逆的功能障碍，这种中断是由脱髓鞘、轴突变性和突触丧失引起的。此外，损伤脊髓中产生的难治性底物会抑制自发恢复。中枢神经系统神经元在适宜环境中的再生能力的发现以及脊髓中神经干细胞的证实，一度燃起了治愈SCI的希望。当神经保护药物、细胞移植以及增强髓鞘再生、轴突再生和神经元可塑性的策略在SCI动物模型中显示出显著改善，但却未能转化为对人类患者的治愈方法时，这种希望逐渐被越来越多的挫败感所取代。然而，SCI研究的最新进展极大地增进了我们对SCI潜在基本过程的理解，并增强了人们越来越乐观的情绪，即这些多种治疗策略最终将汇聚在一起，开创一个新的时代，在这个时代我们将能够提出令人鼓舞的疗法，使SCI患者得到明显改善。在这篇综述中，我们概述了使脊髓难以再生的SCI病理生理学，并讨论了细胞替代和生物材料植入策略本身以及作为联合治疗所开展的研究。我们将重点关注这些策略促进神经连接再生的能力，而这种再生对于SCI后实现有意义的功能恢复是必要的。
