General Pathophysiology of Microglia

Microglia, which are the resident innate immune cells of the central nervous system (CNS), have emerged as critical for maintaining health by not only ensuring proper development, activity, and plasticity of neurones and glial cells but also maintaining and restoring homeostasis when faced with various challenges across the lifespan. This chapter is dedicated to the current understanding of microglia, including their beneficial versus detrimental roles, which are highly complex, rely on various microglial states, and intimately depend on their spatiotemporal context. Microglia are first contextualized within the perspective of finding therapeutic strategies to cure diseases in the twenty-first century-the overall functions of neuroglia with relation one to another and to neurones, and their shared CNS environment. A historical framework is provided, and the main principles of glial neuropathology are enunciated. The current view of microglial nomenclature is then covered, notably by discussing the rejected concepts of microglial activation, their polarisation into M1 and M2 phenotypes, and neuroinflammation. The transformation of the microglial population through the addition, migration, and elimination of individual members, as well as their dynamic metamorphosis between a wide variety of structural and functional states, based on the experienced physiological and pathological stimuli, is subsequently discussed. Lastly, the perspective of microglia as a cell type endowed with a health status determining their outcomes on adaptive CNS plasticity as well as disease pathology is proposed for twenty-first-century approaches to disease prevention and treatment.