Microglia: Multiple roles in surveillance, circuit shaping, and response to injury

Microglial cells are the immune cells in the CNS and represent approximately 10% of the total brain cell population. Their morphologic characterization by Pio del Rio-Hortega was first published almost a century ago, but the understanding of their function in the normal and injured CNS is still incomplete. Classically, microglia have been classified into 2 main types: "resting" microglia, with a ramified morphology, present in the uninjured CNS; and "activated" microglia, with an amoeboid morphology, present at the sites of injury. However, morphologic, molecular, and genetic studies indicate that this subdivision is a misleading oversimplification. Resting microglia actively survey their environment; activated microglia constitute a heterogeneous population that dynamically changes in phenotype depending on the type of stimulus and microenvironment, participating not only in mechanisms of injury but also in neuroprotection, repair, and circuit refinement in the CNS. The primary role of microglia is therefore to maintain cellular, synaptic, and myelin homeostasis both during development and normal function of the CNS and in response to CNS injury. Microglia have been implicated in mechanisms of CNS trauma, stroke, infection, demyelination, neoplasm, and neurodegeneration. Microglial dysfunction may also contribute to genetic neurobehavioral disorders, such as Rett syndrome. There are several comprehensive reviews on all these topics.