Inserm U1130, CNRS UMR 8246, neurosciences Paris Seine, faculté des sciences UPMC, institut de biologie Paris-Seine, Sorbonne université, 75005 Paris, France.
Rev Neurol (Paris). 2020 May;176(4):252-260. doi: 10.1016/j.neurol.2019.07.029. Epub 2020 Jan 22.
As a part of the central nervous system (CNS), the adult mammalian spinal cord displays only very poor ability for self-repair in response to traumatic lesions, which mostly lead to more or less severe, life-long disability. While even adult CNS neurons have a certain plastic potential, their intrinsic regenerative capacity highly varies among different neuronal populations and in the end, regeneration is almost completely inhibited due to extrinsic factors such as glial scar and cystic cavity formation, excessive and persistent inflammation, presence of various inhibitory molecules, and absence of trophic support and of a growth-supportive extracellular matrix structure. In recent years, a number of experimental animal models have been developed to overcome these obstacles. Since all those studies based on a single approach have yielded only relatively modest functional recovery, it is now consensus that different therapeutic approaches will have to be combined to synergistically overcome the multiple barriers to CNS regeneration, especially in humans. In this review, we particularly emphasize the hope raised by the development of novel, implantable biomaterials that should favor the reconstruction of the damaged nervous tissue, and ultimately allow for functional recovery of sensorimotor functions. Since human spinal cord injury pathology depends on the vertebral level and the severity of the traumatic impact, and since the timing of application of the different therapeutic approaches appears very important, we argue that every case will necessitate individual evaluation, and specific adaptation of therapeutic strategies.
作为中枢神经系统(CNS)的一部分,成年哺乳动物脊髓在应对创伤性损伤时表现出非常差的自我修复能力,这主要导致或多或少严重的、终身残疾。虽然即使是成年中枢神经系统神经元也具有一定的可塑性潜力,但它们的内在再生能力在不同神经元群体之间存在很大差异,最终由于外在因素(如胶质瘢痕和囊性腔形成、过度和持续的炎症、存在各种抑制分子以及缺乏营养支持和生长支持的细胞外基质结构),再生几乎完全受到抑制。近年来,已经开发了许多实验动物模型来克服这些障碍。由于所有基于单一方法的研究仅产生了相对适度的功能恢复,因此现在人们一致认为,必须结合不同的治疗方法来协同克服中枢神经系统再生的多种障碍,尤其是在人类中。在这篇综述中,我们特别强调了新型可植入生物材料的发展所带来的希望,这些材料应该有利于受损神经组织的重建,并最终允许感觉运动功能的恢复。由于人类脊髓损伤病理取决于椎体水平和创伤性冲击的严重程度,并且不同治疗方法的应用时机似乎非常重要,因此我们认为每个病例都需要进行个体化评估,并对治疗策略进行具体调整。