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CNS border-associated macrophages in the homeostatic and ischaemic brain
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2022-06-03 , DOI: 10.1016/j.pharmthera.2022.108220
Gabriela Gerganova 1 , Alexandra Riddell 1 , Alyson A Miller 1
Affiliation  

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.



中文翻译:

稳态和缺血脑中的 CNS 边界相关巨噬细胞

CNS 边界相关巨噬细胞 (BAM) 是一小群专门的巨噬细胞,位于脉络丛、脑膜和血管周围空间。直到最近,人们对这种难以捉摸的细胞类型的功能知之甚少,而且在很大程度上被忽视了,特别是与小胶质细胞(主要的大脑常驻免疫细胞)相比。然而,最近对稳态大脑中 BAM 子集的单细胞免疫表型分析或转录组学分析,再加上探索 BAM 在各种脑病变中的功能的新研究的迅速出现,包括阿尔茨海默病、高血压引起的神经血管和认知功能障碍以及缺血性中风,揭示了 BAM 人群以前未被认识到的异质性和时空复杂性,以及它们对大脑稳态和疾病的贡献。在这篇评论中,我们讨论了这一新发现的知识对我们目前对缺血性中风中 BAM 功能的理解的影响。我们首先全面概述和讨论最近研究中描述的稳态 BAM 子集的细胞表面表达谱、转录特征和潜在功能表型。检查了它们推定的生理作用的证据,包括它们参与免疫监视、废物清除和血管通透性。我们讨论了支持 BAM 积累和遗传转化以应对缺血的证据,并评估了 BAM 功能在中风急性期可能有害的实验证据,同时考虑了 BAM 可能影响中风预后的长期机制。最后,

更新日期:2022-06-03
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