There are several cellular and acellular structural barriers associated with the brain interfaces, which include the dura, the leptomeninges, the perivascular space and the choroid plexus epithelium. Each structure is enriched by distinct myeloid populations, which mainly originate from erythromyeloid precursors (EMP) in the embryonic yolk sac and seed the CNS during embryogenesis. However, depending on the precise microanatomical environment, resident myeloid cells differ in their marker profile, turnover and the extent to which they can be replenished by blood-derived cells. While some EMP-derived cells seed the parenchyma to become microglia, others engraft the meninges and become CNS-associated macrophages (CAMs), also referred to as border-associated macrophages (BAMs), e.g., leptomeningeal macrophages (MnMΦ). Recent data revealed that MnMΦ migrate into perivascular spaces postnatally where they differentiate into perivascular macrophages (PvMΦ). Under homeostatic conditions in pathogen-free mice, there is virtually no contribution of bone marrow-derived cells to MnMΦ and PvMΦ, but rather to macrophages of the choroid plexus and dura. In neuropathological conditions in which the blood–brain barrier is compromised, however, an influx of bone marrow-derived cells into the CNS can occur, potentially contributing to the pool of CNS myeloid cells. Simultaneously, resident CAMs may also proliferate and undergo transcriptional and proteomic changes, thereby, contributing to the disease outcome. Thus, both resident and infiltrating myeloid cells together act within their microenvironmental niche, but both populations play crucial roles in the overall disease course. Here, we summarize the current understanding of the sources and fates of resident CAMs in health and disease, and the role of the microenvironment in influencing their maintenance and function.

有几种与脑界面相关的细胞和非细胞结构屏障，包括硬脑膜、软脑膜、血管周围空间和脉络丛上皮。每个结构都富含不同的骨髓细胞群，这些细胞群主要起源于胚胎卵黄囊中的红骨髓前体细胞（EMP），并在胚胎发生过程中为中枢神经系统播种。然而，根据精确的微观解剖环境，常驻骨髓细胞的标记谱、周转率以及它们可以被血液来源细胞补充的程度有所不同。虽然一些 EMP 衍生细胞在实质中播种成为小胶质细胞，但其他细胞植入脑膜并成为 CNS 相关巨噬细胞 (CAM)，也称为边界相关巨噬细胞 (BAM)，例如软脑膜巨噬细胞 (MnMΦ)。最近的数据显示，MnMΦ 在出生后迁移到血管周围空间，并在那里分化为血管周围巨噬细胞 (PvMΦ)。在无病原体小鼠的稳态条件下，骨髓来源的细胞实际上对 MnMΦ 和 PvMΦ 没有贡献，而是对脉络丛和硬脑膜的巨噬细胞有贡献。然而，在血脑屏障受损的神经病理条件下，骨髓来源的细胞可能会涌入中枢神经系统，从而可能导致中枢神经系统骨髓细胞库的形成。同时，驻留的 CAM 也可能增殖并经历转录和蛋白质组变化，从而导致疾病结果。因此，常驻和浸润的骨髓细胞在其微环境生态位内共同发挥作用，但这两个群体在整个疾病过程中都发挥着至关重要的作用。在这里，我们总结了目前对健康和疾病中常驻 CAM 的来源和命运的理解，以及微环境在影响其维持和功能中的作用。