Salvador Andrea Francesca M, Kipnis Jonathan
Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22908, USA.
Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Semin Immunol. 2022 Jan;59:101629. doi: 10.1016/j.smim.2022.101629. Epub 2022 Jun 24.
Traumatic injuries of the central nervous system (CNS) affect millions of people worldwide, and they can lead to severely damaging consequences such as permanent disability and paralysis. Multiple factors can obstruct recovery after CNS injury. One of the most significant is the progressive neuronal death that follows the initial mechanical impact, leading to the loss of undamaged cells via a process termed secondary neurodegeneration. Efforts to define treatments that limit the spread of damage, while important, have been largely ineffectual owing to gaps in the mechanistic understanding that underlies the persisting neuronal cell death. Inflammation, with its influx of immune cells that occurs shortly after injury, has been associated with secondary neurodegeneration. However, the role of the immune system after CNS injury is far more complex. Studies have indicated that the immune response after CNS injury is detrimental, owing to immune cell-produced factors (e.g., pro-inflammatory cytokines, free radicals, neurotoxic glutamate) that worsen tissue damage. Our lab and others have also demonstrated the beneficial immune response that occurs after CNS injury, with the release of growth factors such as brain-derived growth factor (BDNF) and interleukin (IL-10) and the clearance of apoptotic and myelin debris by immune cells. In this review, we first discuss the multifaceted roles of the immune system after CNS injury. We then speculate on how advancements in single-cell RNA technologies can dramatically change our understanding of the immune response, how the spinal cord meninges serve as an important site for hosting immunological processes critical for recovery, and how the origin of peripherally recruited immune cells impacts their function in the injured CNS.
中枢神经系统（CNS）创伤性损伤影响着全球数百万人，并可能导致严重的破坏性后果，如永久性残疾和瘫痪。多种因素会阻碍中枢神经系统损伤后的恢复。其中最重要的因素之一是初始机械冲击后发生的进行性神经元死亡，通过一个称为继发性神经变性的过程导致未受损细胞的丧失。尽管确定限制损伤扩散的治疗方法很重要，但由于对持续神经元细胞死亡背后的机制理解存在差距，这些努力在很大程度上是无效的。炎症在损伤后不久会有免疫细胞涌入，它与继发性神经变性有关。然而，中枢神经系统损伤后免疫系统的作用要复杂得多。研究表明，中枢神经系统损伤后的免疫反应是有害的，因为免疫细胞产生的因子（如促炎细胞因子、自由基、神经毒性谷氨酸）会加重组织损伤。我们实验室和其他实验室也证明了中枢神经系统损伤后发生的有益免疫反应，包括脑源性神经营养因子（BDNF）和白细胞介素（IL-10）等生长因子的释放，以及免疫细胞对凋亡和髓鞘碎片的清除。在这篇综述中，我们首先讨论中枢神经系统损伤后免疫系统的多方面作用。然后，我们推测单细胞RNA技术的进步如何能极大地改变我们对免疫反应的理解，脊髓脑膜如何作为一个重要部位承载对恢复至关重要的免疫过程，以及外周募集的免疫细胞的起源如何影响它们在受损中枢神经系统中的功能。
