CNS border-associated macrophages in the homeostatic and ischaemic brain

Gerganova, G., Riddell, A. and Miller, A. A. (2022) CNS border-associated macrophages in the homeostatic and ischaemic brain. Pharmacology and Therapeutics, 240, 108220. (doi: 10.1016/j.pharmthera.2022.108220) (PMID:35667516)

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CNS border-associated macrophages (BAMs) are a small population of specialised macrophages localised in the choroid plexus, meningeal and perivascular spaces. Until recently, the function of this elusive cell type was poorly understood and largely overlooked, especially in comparison to microglia, the primary brain resident immune cell. However, the recent single cell immunophenotyping or transcriptomic analysis of BAM subsets in the homeostatic brain, coupled with the rapid emergence of new studies exploring BAM functions in various cerebral pathologies, including Alzheimer's disease, hypertension-induced neurovascular and cognitive dysfunction, and ischaemic stroke, has unveiled previously unrecognised heterogeneity and spatial-temporal complexity in BAM populations as well as their contributions to brain homeostasis and disease. In this review, we discuss the implications of this new-found knowledge on our current understanding of BAM function in ischaemic stroke. We first provide a comprehensive overview and discussion of the cell-surface expression profiles, transcriptional signatures and potential functional phenotypes of homeostatic BAM subsets described in recent studies. Evidence for their putative physiological roles is examined, including their involvement in immunological surveillance, waste clearance, and vascular permeability. We discuss the evidence supporting the accumulation and genetic transformation of BAMs in response to ischaemia and appraise the experimental evidence that BAM function might be deleterious in the acute phase of stroke, while considering the mechanisms by which BAMs may influence stroke outcomes in the longer term. Finally, we review the therapeutic potential of immunomodulatory strategies as an approach to stroke management, highlighting current challenges in the field and key issues relating to BAMs, and how BAMs could be harnessed experimentally to support future translational research.

Item Type:Articles
Additional Information:The authors acknowledge the British Heart Foundation for their financial support: 4-year PhD Programme: FS/18/58/34179 to GG; and the University of Glasgow Centre of Excellence Award: RE/13/5/3017.
Glasgow Author(s) Enlighten ID:Miller, Dr Alyson and Gerganova, Gabriela and Riddell, Dr Alexandra
Authors: Gerganova, G., Riddell, A., and Miller, A. A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Pharmacology and Therapeutics
ISSN (Online):1879-016X
Published Online:03 June 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Pharmacology and Therapeutics 240: 108220
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
305659BHF 4-Year PhD Studentship Award 2018Rhian TouyzBritish Heart Foundation (BHF)FS/18/58/34179CAMS - Cardiovascular Science
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences