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Updated: Jul 29, 2025

Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
CNS Border-Associated Macrophages: Ontogeny and Potential Implication in Disease
Iasonas Dermitzakis1, Paschalis Theotokis1, Paschalis Evangelidis1
1Department of Histology-Embryology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Insights
Border-associated macrophages (BAMs) are crucial for central nervous system (CNS) health but their origins and roles are not fully understood. This review explores BAM development and involvement in CNS diseases for targeted therapies.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Neuroscience
Background:
- The central nervous system (CNS) possesses unique immune cells, including microglia and border-associated macrophages (BAMs).
- BAMs reside in specific CNS compartments (choroid plexus, meningeal, perivascular spaces) and are distinct from microglia.
- While microglial ontogeny is well-studied, BAMs require further investigation due to their recent discovery and unique characteristics.
Purpose of the Study:
- To review the current understanding of border-associated macrophage (BAM) ontogeny.
- To explore the role of BAMs in the context of central nervous system (CNS) diseases.
- To highlight the potential of BAMs in developing targeted therapeutic strategies and precision medicine.
Main Methods:
- Review of recent scientific literature and emerging techniques.
- Analysis of data on BAM cellular heterogeneity and diversity.
- Examination of ontogenetic origins and repopulation patterns of BAMs.
Main Results:
- Recent findings indicate BAMs originate from yolk sac progenitors, distinct from bone marrow-derived monocytes.
- Advanced techniques reveal significant cellular heterogeneity and diversity within BAM populations.
- BAMs are increasingly recognized for their involvement in neurodegenerative and neuroinflammatory disease processes.
Conclusions:
- Further research into BAM ontogeny and molecular drivers is essential for defining their cellular identity.
- Understanding BAMs is critical for advancing therapeutic strategies in CNS diseases.
- BAMs represent a promising target for precision medicine approaches in neurological disorders.
Abstract:
Being immune privileged, the central nervous system (CNS) is constituted by unique parenchymal and non-parenchymal tissue-resident macrophages, namely, microglia and border-associated macrophages (BAMs), respectively. BAMs are found in the choroid plexus, meningeal and perivascular spaces, playing critical roles in maintaining CNS homeostasis while being phenotypically and functionally distinct from microglial cells. Although the ontogeny of microglia has been largely determined, BAMs need comparable scrutiny as they have been recently discovered and have not been thoroughly explored. Newly developed techniques have transformed our understanding of BAMs, revealing their cellular heterogeneity and diversity. Recent data showed that BAMs also originate from yolk sac progenitors instead of bone marrow-derived monocytes, highlighting the absolute need to further investigate their repopulation pattern in adult CNS. Shedding light on the molecular cues and drivers orchestrating BAM generation is essential for delineating their cellular identity. BAMs are receiving more attention since they are gradually incorporated into neurodegenerative and neuroinflammatory disease evaluations. The present review provides insights towards the current understanding regarding the ontogeny of BAMs and their involvement in CNS diseases, paving their way into targeted therapeutic strategies and precision medicine.

