Division of Translational and Experimental Neuroscience, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Human Biology Program, University of Toronto, Wetmore Hall, 300 Huron St., Room 105, Toronto, Ontario M5S 3J6, Canada.
Exp Neurol. 2021 Jul;341:113704. doi: 10.1016/j.expneurol.2021.113704. Epub 2021 Mar 19.
Spinal cord injury (SCI) has a complex pathophysiology. Following the initial physical trauma to the spinal cord, which may cause vascular disruption, hemorrhage, mechanical injury to neural structures and necrosis, a series of biomolecular cascades is triggered to evoke secondary injury. Neuroinflammation plays a major role in the secondary injury after traumatic SCI. To date, the administration of systemic immunosuppressive medications, in particular methylprednisolone sodium succinate, has been the primary pharmacological treatment. This medication is given as a complement to surgical decompression of the spinal cord and maintenance of spinal cord perfusion through hemodynamic augmentation. However, the impact of neuroinflammation is complex with harmful and beneficial effects. The use of systemic immunosuppressants is further complicated by the natural onset of post-injury immunosuppression, which many patients with SCI develop. It has been hypothesized that immunomodulation to attenuate detrimental aspects of neuroinflammation after SCI, while avoiding systemic immunosuppression, may be a superior approach. To accomplish this, a detailed understanding of neuroinflammation and the systemic immune responses after SCI is required. Our review will strive to achieve this goal by first giving an overview of SCI from a clinical and basic science context. The role that neuroinflammation plays in the pathophysiology of SCI will be discussed. Next, the positive and negative attributes of the innate and adaptive immune systems in neuroinflammation after SCI will be described. With this background established, the currently existing immunosuppressive and immunomodulatory therapies for treating SCI will be explored. We will conclude with a summary of topics that can be explored by neuroimmunology research. These concepts will be complemented by points to be considered by neuroscientists developing therapies for SCI and other injuries to the central nervous system.
脊髓损伤（SCI）具有复杂的病理生理学。在脊髓受到最初的物理创伤后，可能会导致血管破裂、出血、神经结构的机械损伤和坏死，一系列生物分子级联反应被触发，引发继发性损伤。神经炎症在创伤性 SCI 后的继发性损伤中起主要作用。迄今为止，全身免疫抑制药物的给药，特别是甲泼尼龙琥珀酸钠，一直是主要的药理学治疗方法。这种药物与脊髓的手术减压以及通过血液动力学增强来维持脊髓灌注一起使用。然而，神经炎症的影响很复杂，既有有害的，也有有益的。全身免疫抑制剂的使用因受伤后自然发生的免疫抑制而变得更加复杂，许多 SCI 患者都会出现这种情况。人们假设，通过免疫调节来减轻 SCI 后神经炎症的有害方面，同时避免全身免疫抑制，可能是一种更好的方法。为了实现这一目标，需要详细了解 SCI 后的神经炎症和全身免疫反应。我们的综述将通过首先从临床和基础科学的角度概述 SCI 来努力实现这一目标。将讨论神经炎症在 SCI 病理生理学中的作用。接下来，将描述 SCI 后固有和适应性免疫系统在神经炎症中的积极和消极属性。在建立了这一背景之后，将探讨目前用于治疗 SCI 的免疫抑制和免疫调节疗法。我们将以神经免疫学研究可以探讨的主题的总结作为结束。这些概念将辅以神经科学家为 SCI 和中枢神经系统其他损伤开发治疗方法时需要考虑的要点。
