Microglial cells are the most prominent immune cells of the central nervous system (CNS) and are the first to respond when something goes wrong in the brain. The microglial population accounts for approximately 10% of the cells in the whole brain. Over the years, the immune functions of these cells have attracted attention due to their involvement in virtually all pathological processes in the brain, including inflammation, stroke, neurodegenerative diseases, and viral and bacterial infection. However, their role in supporting cognitive processes and homeostasis in the healthy adult brain is only beginning to be understood, with recent studies generating striking new information for the field.
Microglia as the most potent antigen-presenting cell population in the central nervous system (CNS), serving different functional roles and existing in three distinct forms of ramified microglia, reactive microglia and amoeboid microglia
Ramified (resting) microglia have been reported to be the predominant type of microglia in the fetal and infant CNS. This type of microglial cell may contribute to metabolite CNS repair by removal and clearance of toxins released from injured neurons. In the typical brain, ramified microglia are considered the resting microglia, but findings suggest that they are the most sensitive sensors for pathological events in the CNS. In fact, ramified cells are considered the first line of defence within the brain and undergo proliferation in response to certain types of neuronal injury.(64) Upon the detection of any brain lesion or dysfunction or inflammatory signal, they acquire an “activated” state which displays inflammatory and phagocytic features.
In response to pathologic conditions in the brain, such as hypoxia and/or ischaemia, the quiescent ramified microglia proliferate and differentiate into active “brain macrophages” known as reactive microglia. Reactive microglia contain numerous lysosomes and phagosomes and become activated following brain ischemia, injury and neuroinflammation. Following a damaging event, reactive microglia accumulate at the site of injury, where they play a neuroprotective role in phagocytosing damaged cells and debris. Like macrophages, reactive microglia secrete inflammatory mediators, which orchestrate the cerebral immune response. Chronic microglial activation is associated with sustained secretion of inflammatory mediators, and is thought to have a deleterious effect on neuronal function and survival.
Amoeboid microglia are associated with the developing fetal CNS by secreting several proteins, including inflammatory cytokines and neurotrophic factors, which regulate brain homeostasis during development. Amoeboid microglia are found in the fetal brain, from around 46 days of gestation in sheep, and ultimately in the adult CNS, they grow and transdifferentiate into ramified microglia. Amoeboid microglia contain a small round cell body indicative of a motile phagocytic phenotype with proliferative, and migratory trait. The amoeboid microglia play a role in axonal migration and growth and tissue histogenesis through the removal of inappropriate and dead axons.