Department of Neurological Surgery, School of Medicine and Public Health (UWSMPH), University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA.
J Neuroinflammation. 2021 Dec 7;18(1):284. doi: 10.1186/s12974-021-02337-2.
Traumatic spinal cord injury (SCI) is a devastating neurological condition that results in a loss of motor and sensory function. Although extensive research to develop treatments for SCI has been performed, to date, none of these treatments have produced a meaningful amount of functional recovery after injury. The primary injury is caused by the initial trauma to the spinal cord and results in ischemia, oxidative damage, edema, and glutamate excitotoxicity. This process initiates a secondary injury cascade, which starts just a few hours post-injury and may continue for more than 6 months, leading to additional cell death and spinal cord damage. Inflammation after SCI is complex and driven by a diverse set of cells and signaling molecules. In this review, we utilize an extensive literature survey to develop the timeline of local immune cell and cytokine behavior after SCI in rodent models. We discuss the precise functional roles of several key cytokines and their effects on a variety of cell types involved in the secondary injury cascade. Furthermore, variations in the inflammatory response between rats and mice are highlighted. Since current SCI treatment options do not successfully initiate functional recovery or axonal regeneration, identifying the specific mechanisms attributed to secondary injury is critical. With a more thorough understanding of the complex SCI pathophysiology, effective therapeutic targets with realistic timelines for intervention may be established to successfully attenuate secondary damage.
创伤性脊髓损伤（SCI）是一种毁灭性的神经系统疾病，导致运动和感觉功能丧失。尽管已经进行了广泛的研究来开发 SCI 的治疗方法，但迄今为止，这些治疗方法都没有在损伤后产生有意义的功能恢复。原发性损伤是由脊髓的初始创伤引起的，导致缺血、氧化损伤、水肿和谷氨酸兴奋性毒性。这一过程引发了继发性损伤级联反应，该反应在损伤后几个小时内开始，可能持续 6 个月以上，导致更多的细胞死亡和脊髓损伤。SCI 后的炎症反应复杂，由多种细胞和信号分子驱动。在这篇综述中，我们利用广泛的文献调查来制定 SCI 后啮齿动物模型中局部免疫细胞和细胞因子行为的时间线。我们讨论了几种关键细胞因子的确切功能作用及其对继发性损伤级联反应中涉及的多种细胞类型的影响。此外，还强调了大鼠和小鼠之间炎症反应的差异。由于目前的 SCI 治疗选择不能成功地启动功能恢复或轴突再生，因此确定与继发性损伤相关的特定机制至关重要。通过更深入地了解复杂的 SCI 病理生理学，可以确定具有现实干预时间框架的有效治疗靶点，以成功减轻继发性损伤。
