Even though several highly effective treatments have been developed for multiple sclerosis (MS), the underlying pathological mechanisms and drivers of the disease have not been fully elucidated. In recent years, there has been a growing interest in studying neuroinflammation in the context of glial cell involvement as there is increasing evidence of their central role in disease progression. Although glial cell communication and proper function underlies brain homeostasis and maintenance, their multiple effects in an MS brain remain complex and controversial. In this review, we aim to provide an overview of the contribution of glial cells, oligodendrocytes, astrocytes, and microglia in the pathology of MS during both the activation and orchestration of inflammatory mechanisms, as well as of their synergistic effects during the repair and restoration of function. Additionally, we discuss how the understanding of glial cell involvement in MS may provide new therapeutic targets either to limit disease progression or to facilitate repair.

Oligodendrocytes are the myelin forming cells throughout the central nervous system (CNS) and make up around 5–10% of all glia cells. They are fundamental not only to myelin formation during CNS development, but also critical for preserving the homeostasis of myelin and axons in the mature CNS, as well as for myelin regeneration following injury, inflammation and other pathologies. Their dynamic interaction with axons and other glia, especially astrocytes, as well as their participation in the network of cell connectivity known as panglial syncytium, facilitates their roles and the overall integrity of the CNS. Their crucial functions have been revealed by the discovery of characteristic genetic and acquired disorders that impair different stages of their development and connectivity. This chapter highlights some of the key features of oligodendrocytes and their positioning as key elements in the CNS panglial syncytium. <!----> <!----> <!----> <!---->