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Proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of parenchymal sentinels referred to as microglia. Although microglia were first described as ramified brain-resident phagocytes, research conducted over the past century has expanded considerably upon this narrow view and ascribed many functions to these dynamic CNS inhabitants. Microglia are now considered among the most versatile cells in the body, possessing the capacity to morphologically and functionally adapt to their ever-changing surroundings. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Microglia are in fact vital participants in CNS homeostasis, and dysregulation of these sentinels can give rise to neurological disease. In this review, we discuss the exciting developments in our understanding of microglial biology, from their developmental origin to their participation in CNS homeostasis and pathophysiological states such as neuropsychiatric disorders, neurodegeneration, sterile injury responses, and infectious diseases. We also delve into the world of microglial dynamics recently uncovered using real-time imaging techniques.
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Supplemental Video a1: Naive microglia possess multiple, highly ramified processes extending in all directions. Supplemental Video a2: Naive microglia possess multiple, highly ramified processes extending in all directions. Supplemental Video b: Upon diffuse activation induced by CNS viral infection with LCMV, microglial processes become shorter and less complex than naive microglia but retain a ramified structure. Supplemental Video c: Upon focal activation induced by a meningeal compression injury, microglia directionally extend multiple processes toward the focal site of injury, concurrently retracting processes in all other directions. Supplemental Video d: In response to damage at or above the glial limitans, astrocytes recruit microglial processes that line the borders between individual cells to form a continuous, honeycomb-like network composed of processes from numerous individual microglia. Supplemental Video e: In response to necrotic cell death, microglia become phagocytic and sometimes motile by first extending a single large circular extension toward the injured cell while retracting all other processes. The microglia soma is eventually pulled into the phagocytic extension along the thin connecting process.
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