Figure 2.

(a) Schematic representation of microglial development: Microglia are derived from c-kit-positive erythromyeloid precursors (EMPs) in the yolk sac at E7.5–E8.0. These precursors develop into CD45⁺ c-kit^low CX₃CR1⁻ immature (A1) cells and mature into CD45⁺ c-kit⁻ CX₃CR1⁺ (A2) cells. Proliferating A2 cells develop into embryonic microglia. Before completion of the blood–brain barrier (BBB), they invade the developing brain in a manner requiring matrix metalloproteinase (MMP) activity at E9.5. A2 cells colonize the brain tissue to establish a population of mature microglia. By contrast, blood monocytes are derived from hematopoietic stem cells (HSCs). Unless the BBB is disrupted, microglia and monocytes are independent of each other in the postnatal stage. (b) Multiple roles of microglia in the postnatal brain: Microglia in the postnatal brain are multifunctional. Primarily, they are involved in immune surveillance, and when necessary, they initiate an inflammatory response. Although this contributes to the elimination of pathogens, an excessive inflammatory response may result in bystander tissue damage. Microglia also phagocytose pathogens and apoptotic neurons and exert scavenging actions on tissue debris under pathological conditions. Microglia recognizes apoptotic cells by phosphatidylserine and other apoptotic signals. With regard to synaptic refinement, they carry out synaptic pruning in a manner requiring C3-C3R interactions. Microglia execute synaptic formation by secreting BDNF. In addition, microglia-derived TNFα can exert neuroprotective as well as neurodestructive action within different contexts.⁷⁴ Microglia also play a role in angiogenesis through by synthesizing vascular endothelial growth factor (VEGF).⁷⁵