Different tissue-resident macrophages are present in and at the borders of the brain. Microglia reside in the central nervous system parenchyma, whereas non-parenchymal macrophages dwell at the interface between the brain and the periphery, including the perivascular spaces, the choroid plexus, and the meninges. Microglia display regional heterogeneity in phenotype and function, and fulfill critical roles in neuronal development and regulation of brain homeostasis in the healthy brain. In recent years, it became clear that the non-parenchymal macrophages also exhibit transcriptional diversity and different dynamics but less is known about their functional specification at their respective anatomical locations. This review discusses recent advances describing the heterogeneity of the brain macrophage compartment and potential physiological functions with a focus on non-parenchymal macrophages.
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