Ludwin Samuel K, Rao Vijayaraghava Ts, Moore Craig S, Antel Jack P
Neuroimmunology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada/Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Neuroimmunology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Mult Scler. 2016 Aug;22(9):1114-24. doi: 10.1177/1352458516643396. Epub 2016 Apr 19.
Recent experimental and clinical studies on astrocytes are unraveling the capabilities of these multi-functional cells in normal homeostasis, and in central nervous system (CNS) disease. This review focuses on understanding their behavior in all aspects of the initiation, evolution, and resolution of the multiple sclerosis (MS) lesion. Astrocytes display remarkable flexibility and variability of their physical structure and biochemical output, each aspect finely tuned to the specific stage and location of the disease, participating in both pathogenic and beneficial changes seen in acute and progressive forms. As examples, chemo-attractive or repulsive molecules may facilitate the entry of destructive immune cells but may also aid in the recruitment of oligodendrocyte precursors, essential for repair. Pro-inflammatory cytokines may attack pathogenic cells and also destroy normal oligodendrocytes, myelin, and axons. Protective trophic factors may also open the blood-brain barrier and modulate the extracellular matrix to favor recruitment and persistence of CNS-specific immune cells. A chronic glial scar may confer structural support following tissue loss and inhibit ingress of further noxious insults and also inhibit migration of reparative cells and molecules into the damaged tissue. Continual study into these processes offers the therapeutic opportunities to enhance the beneficial capabilities of these cells while limiting their destructive effects.
近期关于星形胶质细胞的实验和临床研究正在揭示这些多功能细胞在正常内环境稳态以及中枢神经系统（CNS）疾病中的能力。本综述着重于了解它们在多发性硬化症（MS）病变的起始、演变和消退的各个方面的行为。星形胶质细胞在其物理结构和生化输出方面表现出显著的灵活性和变异性，每个方面都与疾病的特定阶段和位置精确匹配，参与急性和进展性形式中所见的致病和有益变化。例如，化学吸引或排斥分子可能促进破坏性免疫细胞的进入，但也可能有助于招募对修复至关重要的少突胶质细胞前体。促炎细胞因子可能攻击致病细胞，但也会破坏正常的少突胶质细胞、髓鞘和轴突。保护性营养因子也可能打开血脑屏障并调节细胞外基质，以利于中枢神经系统特异性免疫细胞的募集和存留。慢性胶质瘢痕可能在组织损失后提供结构支持，抑制进一步有害损伤的侵入，同时也抑制修复性细胞和分子向受损组织的迁移。对这些过程的持续研究提供了治疗机会，以增强这些细胞的有益能力，同时限制其破坏作用。
