Kong Xiangyi, Gao Jun
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA, USA.
J Cell Mol Med. 2017 May;21(5):941-954. doi: 10.1111/jcmm.13034. Epub 2016 Dec 13.
Acute spinal cord injury (SCI) has become epidemic in modern society. Despite advances made in the understanding of the pathogenesis and improvements in early recognition and treatment, it remains a devastating event, often producing severe and permanent disability. SCI has two phases: acute and secondary. Although the acute phase is marked by severe local and systemic events such as tissue contusion, ischaemia, haemorrhage and vascular damage, the outcome of SCI are mainly influenced by the secondary phase. SCI causes inflammatory responses through the activation of innate immune responses that contribute to secondary injury, in which polarization-based macrophage activation is a hallmarker. Macrophages accumulated within the epicentre and the haematoma of the injured spinal cord play a significant role in this inflammation. Depending on their phenotype and activation status, macrophages may initiate secondary injury mechanisms and/or promote CNS regeneration and repair. When it comes to therapies for SCI, very few can be performed in the acute phase. However, as macrophage activation and polarization switch are exquisitely sensitive to changes in microenvironment, some trials have been conducted to modulate macrophage polarization towards benefiting the recovery of SCI. Given this, it is important to understand how macrophages and SCI interrelate and interact on a molecular pathophysiological level. This review provides a comprehensive overview of the immuno-pathophysiological features of acute SCI mainly from the following perspectives: (i) the overview of the pathophysiology of acute SCI, (ii) the roles of macrophage, especially its polarization switch in acute SCI, and (iii) newly developed neuroprotective therapies modulating macrophage polarization in acute SCI.
急性脊髓损伤（SCI）在现代社会中已成为一种流行病。尽管在发病机制的理解以及早期识别和治疗方面取得了进展，但它仍然是一个具有毁灭性的事件，常常导致严重且永久性的残疾。SCI 有两个阶段：急性期和继发期。虽然急性期的特征是严重的局部和全身事件，如组织挫伤、缺血、出血和血管损伤，但 SCI 的结果主要受继发期影响。SCI 通过激活先天性免疫反应引发炎症反应，这有助于继发性损伤，其中基于极化的巨噬细胞激活是一个标志。积聚在受损脊髓的震中及血肿内的巨噬细胞在这种炎症中起重要作用。根据其表型和激活状态，巨噬细胞可能启动继发性损伤机制和/或促进中枢神经系统的再生与修复。说到 SCI 的治疗方法，在急性期可实施的非常少。然而，由于巨噬细胞激活和极化转换对微环境变化极为敏感，已经开展了一些试验来调节巨噬细胞极化以利于 SCI 的恢复。鉴于此，了解巨噬细胞与 SCI 在分子病理生理水平上如何相互关联和相互作用很重要。本综述主要从以下几个方面全面概述急性 SCI 的免疫病理生理特征：（i）急性 SCI 的病理生理学概述，（ii）巨噬细胞的作用，尤其是其在急性 SCI 中的极化转换，以及（iii）在急性 SCI 中调节巨噬细胞极化的新开发的神经保护疗法。
