PDF(Pubmed)
Abstract：
Deficits in neuronal function are a hallmark of spinal cord injury (SCI) and therapeutic efforts are often focused on central nervous system (CNS) axon regeneration. However, secondary injury responses by astrocytes, microglia, pericytes, endothelial cells, Schwann cells, fibroblasts, meningeal cells, and other glia not only potentiate SCI damage but also facilitate endogenous repair. Due to their profound impact on the progression of SCI, glial cells and modification of the glial scar are focuses of SCI therapeutic research. Within and around the glial scar, cells deposit extracellular matrix (ECM) proteins that affect axon growth such as chondroitin sulfate proteoglycans (CSPGs), laminin, collagen, and fibronectin. This dense deposition of material, i.e., the fibrotic scar, is another barrier to endogenous repair and is a target of SCI therapies. Infiltrating neutrophils and monocytes are recruited to the injury site through glial chemokine and cytokine release and subsequent upregulation of chemotactic cellular adhesion molecules and selectins on endothelial cells. These peripheral immune cells, along with endogenous microglia, drive a robust inflammatory response to injury with heterogeneous reparative and pathological properties and are targeted for therapeutic modification. Here, we review the role of glial and inflammatory cells after SCI and the therapeutic strategies that aim to replace, dampen, or alter their activity to modulate SCI scarring and inflammation and improve injury outcomes.
摘要：
神经元功能的缺陷是脊髓损伤（SCI）的标志，治疗工作通常集中在中枢神经系统（CNS）轴突再生上。然而,星形胶质细胞的继发性损伤反应，小胶质细胞,周细胞,内皮细胞，施万细胞，成纤维细胞,脑膜细胞,和其他胶质细胞不仅增强SCI损伤，而且促进内源性修复。由于对SCI进展的深远影响，神经胶质细胞和神经胶质瘢痕的修饰是SCI治疗研究的重点。神经胶质疤痕内部和周围，细胞沉积影响轴突生长的细胞外基质（ECM）蛋白，如硫酸软骨素蛋白聚糖（CSPGs），层粘连蛋白,胶原蛋白，和纤连蛋白.这种密集的物质沉积，即，纤维化疤痕,是内源性修复的另一个障碍，是SCI治疗的目标。浸润的嗜中性粒细胞和单核细胞通过神经胶质趋化因子和细胞因子释放以及随后在内皮细胞上趋化细胞粘附分子和选择素的上调而被募集到损伤部位。这些外周免疫细胞，以及内源性小胶质细胞，驱动具有异质性修复和病理特性的损伤的强烈炎症反应，并有针对性的治疗修饰。这里,我们回顾了脊髓损伤后神经胶质细胞和炎症细胞的作用，以及旨在替代的治疗策略，阻尼，或改变其活性以调节SCI瘢痕形成和炎症并改善损伤结果。
