Department of Biomedical Engineering, Indian Institute of Technology Ropar, Bara Phool, Punjab, India.
Cell Mol Neurobiol. 2024 Nov 23;44(1):78. doi: 10.1007/s10571-024-01519-9.
Reactive astrogliosis and inflammation are pathologic hallmarks of spinal cord injury. After injury, dysfunction of glial cells (astrocytes) results in glial scar formation, which limits neuronal regeneration. The blood-spinal cord barrier maintains the structural and functional integrity of the spinal cord and does not allow blood vessel components to leak into the spinal cord microenvironment. After the injury, disruption in the spinal cord barrier causes an imbalance of the immunological microenvironment. This triggers the process of neuroinflammation, facilitated by the actions of microglia, neutrophils, glial cells, and cytokines production. Recent work has revealed two phenotypes of astrocytes, A1 and A2, where A2 has a protective type, and A1 releases neurotoxins, further promoting glial scar formation. Here, we first describe the current understanding of the spinal cord microenvironment, both pre-, and post-injury, and the role of different glial cells in the context of spinal cord injury, which forms the essential update on the cellular and molecular events following injury. We aim to explore in-depth signaling pathways and molecular mediators that trigger astrocyte activation and glial scar formation. This review will discuss the activated signaling pathways in astrocytes and other glial cells and their collaborative role in the development of gliosis through inflammatory responses.
反应性星形胶质细胞增生和炎症是脊髓损伤的病理标志。损伤后，神经胶质细胞（星形胶质细胞）功能障碍导致神经胶质瘢痕形成，从而限制神经元再生。血脊髓屏障维持脊髓的结构和功能完整性，不允许血管成分渗漏到脊髓微环境中。损伤后，脊髓屏障的破坏导致免疫微环境失衡。这触发了神经炎症过程，小胶质细胞、中性粒细胞、神经胶质细胞和细胞因子的产生促进了这一过程。最近的研究揭示了星形胶质细胞的两种表型，A1 和 A2，其中 A2 具有保护型，A1 释放神经毒素，进一步促进神经胶质瘢痕形成。在这里，我们首先描述了脊髓微环境在损伤前后的当前理解，以及不同神经胶质细胞在脊髓损伤背景下的作用，这是对损伤后细胞和分子事件的必要更新。我们旨在深入探讨触发星形胶质细胞激活和神经胶质瘢痕形成的信号通路和分子介质。这篇综述将讨论星形胶质细胞和其他神经胶质细胞中的激活信号通路，以及它们通过炎症反应在神经胶质增生中的协同作用。
