Abstract
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.