microglial cell

ORIGIN: Microglia arise from primitive yolk sac myeloid progenitors that colonize the CNS early in embryonic development (mesodermal origin). This contrasts with astrocytes, oligodendrocytes, and ependymal cells (neuroectoderm/neuroepithelial origin), and with peripheral nervous system glia like Schwann cells (neural crest). They self-renew locally and are largely independent of bone marrow replenishment under normal conditions, though blood monocytes can infiltrate in injury or inflammation.

FUNCTIONS: (1) Phagocytosis of debris, apoptotic cells, and pathogens. (2) Antigen presentation via MHC class II. (3) Cytokine and chemokine release (IL-1, IL-6, TNF-α) and reactive oxygen species. (4) Synaptic pruning during development (complement-mediated, C1q/C3 and CR3) and in adult plasticity. (5) Surveillance of the CNS microenvironment. Activated microglia change from a ramified (resting) morphology to an amoeboid phagocytic form.

HISTOLOGY: Small cells with scant cytoplasm and elongated, rod-shaped or comma-shaped nuclei. They are poorly seen on H&E and are best identified by special stains or markers (CD68, Iba1, CD11b). Classically, they are described as "scavenger cells" of the CNS.

CLINICAL SIGNIFICANCE: - Infarction/ischemic stroke: Microglia and recruited macrophages clear necrotic tissue, leading to liquefactive necrosis and a cystic cavity. Macrophages appear about 24-48 hours after injury, with peak activity at days 3-5, and then reactive gliosis (astrocytes) and glial scar formation follow. - HIV: Microglia (and CNS macrophages) are infected by HIV (CD4 and CCR5). Fusion forms multinucleated giant cells characteristic of HIV encephalitis, and the process contributes to HIV-associated neurocognitive disorder. - Neurodegeneration: Chronic microglial activation contributes to Alzheimer disease (microglia cluster around amyloid plaques; TREM2 variants raise risk), Parkinson disease, and multiple sclerosis (they phagocytose myelin; lipid-laden macrophages are present in active plaques). - Prion disease (Creutzfeldt-Jakob disease): Microgliosis accompanies spongiform change, neuronal loss, and astrocytosis. - Neurosyphilis (general paresis): Rod-shaped microglia (Hortega cells) appear in the cortex; the term "rod cells" is a classic association. - Viral encephalitis: Microglial nodules are characteristic of viral infections such as CMV, HIV, and Zika; in rabies, Babes nodules are microglial clusters. - Neuropathic pain and psychiatric disease: Active research areas implicating microglial signaling.

BOARD PEARLS: Microglia = CNS macrophages; mesoderm origin; not part of the blood-brain barrier (astrocyte foot processes, endothelial tight junctions, and pericytes are); HIV-infected cells in the CNS form multinucleated giant cells; first responders in CNS injury, followed by astrocytic gliosis; compare with Kupffer cells (liver), alveolar macrophages (lung), and Langerhans cells (skin) as tissue-resident macrophage equivalents.