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Parenchymal border macrophages

An unnoticed player overseeing CSF flux

Nature Cardiovascular Research volume 1, pages 1114–1115 (2022)Cite this article

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A new study shows that brain-resident parenchymal border macrophages (PBMs) maintain perivascular extracellular matrix composition by the release of matrix metalloproteinases. Depletion of PBMs suppressed glymphatic fluid transport, underscoring their responsibility for perivascular space homeostasis and brain protein clearance.

A fast-growing body of evidence shows that the brain border is a bustling immunological niche, challenging the classical view of the central nervous system (CNS) as an immune-privileged site. Brain tissue is constantly under close immune surveillance for danger signals1. The first line of defense is formed by the parenchymal border macrophages (PBMs), a distinct population of brain‐resident myeloid cells located within the perivascular space surrounding arterioles and venules along the entire brain vasculature2. PBMs also reside in the meningeal and choroid plexuses, which allows them to sample cerebrospinal fluid (CSF)3. It was PBMs’ phagocytic capacity that led to their discovery in 19804, when they were described as granular perithelial cells owing to their distinct uptake of intraventricularly delivered CSF tracers. It is by now established that CNS immune surveillance relies to a large extent on PBMs because of their unique position at the interface between the CNS and peripheral nervous system5. In addition, several reports have suggested that PBMs may have further functional roles. For example, the neurovascular dysfunction in response to amyloid-β has been linked to PBMs6. Yet little is known about the involvement of PBMs in CSF fluid flow. Their close association with the CSF suggests that PBMs may not only regulate blood flow but also control brain fluid transport. In a recent issue of Nature, Drieu et al. explore their possible role in CSF dynamics3.

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Fig. 1: Functions and subtypes of parenchymal border macrophages (PBMs).

References

  1. Papadopoulos, Z., Herz, J. & Kipnis, J. J. Immunol. 204, 286–293 (2020).

    Article  CAS  Google Scholar 

  2. Karam, M., Janbon, H., Malkinson, G. & Brunet, I. J. Cereb. Blood Flow Metab. 42, 1797–1812 (2022).

    Article  CAS  Google Scholar 

  3. Drieu, A. et al. Nature 611, 585–593 (2022).

    Article  CAS  Google Scholar 

  4. Mato, M., Ookawara, S. & Kurihara, K. Am. J. Anat. 157, 329–332 (1980).

    Article  CAS  Google Scholar 

  5. Ousman, S. S. & Kubes, P. Nat. Neurosci. 15, 1096–1101 (2012).

    Article  CAS  Google Scholar 

  6. Park, L. et al. Circ. Res. 121, 258–269 (2017).

    Article  CAS  Google Scholar 

  7. Li, Q. & Barres, B. A. Nat. Rev. Immunol. 18, 225–242 (2018).

    Article  CAS  Google Scholar 

  8. Yunna, C., Mengru, H., Lei, W. & Weidong, C. Macrophage M1/M2 polarization. Eur. J. Pharmacol. 877, 173090 (2020).

    Article  Google Scholar 

  9. Campbell, R. A., Docherty, M.-H., Ferenbach, D. A. & Mylonas, K. J. Front. Immunol. 12, 700790 (2021).

    Article  CAS  Google Scholar 

  10. Clarke, L. E. et al. Proc. Natl Acad. Sci. USA 115, E1896–E1905 (2018).

    CAS  Google Scholar 

  11. Kress, B. T. et al. Ann. Neurol. 76, 845–861 (2014).

    Article  CAS  Google Scholar 

  12. Hawkes, C. A. & McLaurin, J. Proc. Natl Acad. Sci. USA 106, 1261–1266 (2009).

    Article  CAS  Google Scholar 

  13. Elkington, P. T., Green, J. A. & Friedland, J. S. Methods Mol. Biol. 531, 253–265 (2009).

    Article  CAS  Google Scholar 

  14. Thanopoulou, K., Fragkouli, A., Stylianopoulou, F. & Georgopoulos, S. Proc. Natl Acad. Sci. USA 107, 20816–20821 (2010).

    Article  CAS  Google Scholar 

  15. Rasmussen, M. K., Mestre, H. & Nedergaard, M. Lancet Neurol. 17, 1016–1024 (2018).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank D. Xue for expert graphical support. This project has received funding from the Simons Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the US NIH/NINDS/NCCIH (R01AT012312, R01AT011439 and U19 NS128613) and the Novo Nordisk and Lundbeck Foundations, as well as the US Army Research Office (grant MURI W911NF1910280).

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  1. Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark

    Virginia Plá & Maiken Nedergaard

  2. Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA

    Maiken Nedergaard

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  1. Virginia Plá
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Correspondence to Virginia Plá.

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Plá, V., Nedergaard, M. An unnoticed player overseeing CSF flux. Nat Cardiovasc Res 1, 1114–1115 (2022). https://doi.org/10.1038/s44161-022-00176-9

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