Kjell Jacob, Olson Lars
Department of Physiological Genomics, Ludwig-Maximilians-Universität München, Munich 80336, Germany
Department of Neuroscience, Karolinska Institutet, Stockholm 171 77, Sweden
Dis Model Mech. 2016 Oct 1;9(10):1125-1137. doi: 10.1242/dmm.025833.
A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials.
脊髓损伤研究的一个长期目标是为临床开发有效的脊髓修复策略。脊髓损伤的大鼠模型提供了一个重要的哺乳动物模型,可用于评估治疗策略并了解脊髓损伤的病理基础。这些模型推动了用于评估运动和感觉功能恢复的可靠测试的发展。大鼠模型还使我们能够了解脊髓损伤后神经元回路如何变化,以及如何通过增强自发再生机制和对抗内在抑制因子来促进恢复。大鼠研究还揭示了在损伤急性期挽救神经回路和细胞的可能途径。这些模型中的时空和功能研究突出了控制炎症、瘢痕形成和髓鞘形成的治疗潜力。此外,脊髓损伤的潜在替代疗法,包括移植物和桥接物,主要源自大鼠研究。在此,我们讨论大鼠实验性脊髓损伤模型的优缺点,并总结从这些模型中获得的知识。我们还讨论了对不同形式损伤、其病理学和恢复程度的新认识如何激发了众多治疗策略,其中一些已进入临床试验阶段。