Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
Int J Mol Sci. 2021 Sep 8;22(18):9706. doi: 10.3390/ijms22189706.
The pathobiology of traumatic and nontraumatic spinal cord injury (SCI), including degenerative myelopathy, is influenced by neuroinflammation. The neuroinflammatory response is initiated by a multitude of injury signals emanating from necrotic and apoptotic cells at the lesion site, recruiting local and infiltrating immune cells that modulate inflammatory cascades to aid in the protection of the lesion site and encourage regenerative processes. While peripheral immune cells are involved, microglia, the resident immune cells of the central nervous system (CNS), are known to play a central role in modulating this response. Microglia are armed with numerous cell surface receptors that interact with neurons, astrocytes, infiltrating monocytes, and endothelial cells to facilitate a dynamic, multi-faceted injury response. While their origin and essential nature are understood, their mechanisms of action and spatial and temporal profiles warrant extensive additional research. In this review, we describe the role of microglia and the cellular network in SCI, discuss tools for their investigation, outline their spatiotemporal profile, and propose translationally-relevant therapeutic targets to modulate neuroinflammation in the setting of SCI.
创伤性和非创伤性脊髓损伤(SCI)的病理生物学,包括退行性脊髓病,受神经炎症的影响。神经炎症反应是由损伤部位坏死和凋亡细胞发出的多种损伤信号引发的,募集局部和浸润免疫细胞,调节炎症级联反应,以帮助保护损伤部位并促进再生过程。虽然外周免疫细胞参与其中,但小胶质细胞,即中枢神经系统(CNS)的固有免疫细胞,被认为在调节这种反应中起着核心作用。小胶质细胞具有许多细胞表面受体,与神经元、星形胶质细胞、浸润的单核细胞和内皮细胞相互作用,以促进动态的、多方面的损伤反应。虽然它们的起源和本质已经被理解,但它们的作用机制以及时空特征需要广泛的进一步研究。在这篇综述中,我们描述了小胶质细胞和细胞网络在 SCI 中的作用,讨论了用于研究它们的工具,概述了它们的时空特征,并提出了具有转化相关性的治疗靶点,以调节 SCI 中的神经炎症。