Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans

Rajan, Wenson D.; Wojtaś, Bartosz; Gielniewski, Bartłomiej; Miró-Mur, Francesc; Pedragosa, Jordi; Zawadzka, Małgorzata; Pilanc, Paulina; Planas, Anna M.; Kamińska, Bożena

doi:10.1016/j.nbd.2019.104722

Cited by 57 publications

(63 citation statements)

References 42 publications

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“…The dura mater had the highest expression of MHCII+ CD38− cells, while the pia mater and perivascular space had higher levels of MHCII+ CD38 + cells followed by those that were MHCII-CD38 + ; the choroid plexus had a mixture of all three subclasses (Mrdjen et al, 2018). The finding of BAMs and their unique and heterogenous expression has been demonstrated in non-pathological and pathological conditions in mice, with similar findings observed in human brain tissue (Jordao et al, 2019;Rajan et al, 2020).…”

Section: Macrophages and Microglia In Adsupporting

confidence: 65%

“…Recently, a subset of macrophages has been found in the brain called brain associated macrophages (BAMs) (Mrdjen et al, 2018;Villacampa and Heneka, 2018). BAMs are located within the CNS in the border region areas, including the pia mater, perivascular space, choroid plexus, and dura mater and are replaced by circulating monocytes (Park et al, 2017;Mrdjen et al, 2018;Rajan et al, 2020). Through the use of mass cytometry, Mrdjen et al (2018) determined that these cells have an a-typical surface receptor profile, with a high expression of MHCII but neither Ly6C, a myeloid marker, nor Siglec-H, a microglia marker (Mrdjen et al, 2018).…”

Section: Macrophages and Microglia In Admentioning

confidence: 99%

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The Complexity of Microglial Interactions With Innate and Adaptive Immune Cells in Alzheimer’s Disease

Wyatt-Johnson

Brutkiewicz

2020

Front. Aging Neurosci.

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In the naïve mouse brain, microglia and astrocytes are the most abundant immune cells; however, there is a complexity of other immune cells present including monocytes, neutrophils, and lymphocytic cells, such as natural killer (NK) cells, T cells, and B cells. In Alzheimer’s disease (AD), there is high inflammation, reactive microglia, and astrocytes, leaky blood–brain barrier, the buildup of amyloid-beta (Aβ) plaques, and neurofibrillary tangles which attract infiltrating peripheral immune cells that are interacting with the resident microglia. Limited studies have analyzed how these infiltrating immune cells contribute to the neuropathology of AD and even fewer have analyzed their interactions with the resident microglia. Understanding the complexity and dynamics of how these immune cells interact in AD will be important for identifying new and novel therapeutic targets. Thus, this review will focus on discussing our current understanding of how macrophages, neutrophils, NK cells, T cells, and B cells, alongside astrocytes, are altered in AD and what this means for the disorder, as well as how these cells are affected relative to the resident microglia.

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Section: Macrophages and Microglia In Adsupporting

confidence: 65%

Section: Macrophages and Microglia In Admentioning

confidence: 99%

The Complexity of Microglial Interactions With Innate and Adaptive Immune Cells in Alzheimer’s Disease

Wyatt-Johnson

Brutkiewicz

2020

Front. Aging Neurosci.

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“…In addition, the turnover rate for CNS myeloid cells is much slower than peripheral myeloid cells, rendering them more vulnerable to loss of population numbers from toxic insults. It has also been reported that CD163 + BAM are reprogrammed after acute stroke, resulting in leukocyte chemotaxis and neurological impairments 84,85 . Perhaps for these reasons, BAM depletion reduces acute ischemic brain injury.…”

Section: Microglial Polarization and Their Modulatory Mechanisms Aftementioning

confidence: 98%

Microglial/Macrophage polarization and function in brain injury and repair after stroke

et al. 2021

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Stroke is a leading cause of disability and mortality, with limited treatment options. After stroke injury, microglia and CNS‐resident macrophages are rapidly activated and regulate neuropathological processes to steer the course of functional recovery. To accelerate this recovery, microglia can engulf dying cells and clear irreparably‐damaged tissues, thereby creating a microenvironment that is more suitable for the formation of new neural circuitry. In addition, monocyte‐derived macrophages cross the compromised blood‐brain barrier to infiltrate the injured brain. The specific functions of myeloid lineage cells in brain injury and repair are diverse and dependent on phenotypic polarization statuses. However, it remains to be determined to what degree the CNS‐invading macrophages occupy different functional niches from CNS‐resident microglia. In this review, we describe the physiological characteristics and functions of microglia in the developing and adult brain. We also review (a) the activation and phenotypic polarization of microglia and macrophages after stroke, (b) molecular mechanisms that control polarization status, and (c) the contribution of microglia to brain pathology versus repair. Finally, we summarize current breakthroughs in therapeutic strategies that calibrate microglia/macrophage responses after stroke.

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“…Emerging technology and recent publications have demonstrated the usefulness of other quantitative methods that can identify microglial phenotypic changes in humans with high throughput, such as single cell RNAseq and mass cytometry using CyTOF 54 - 56 . RNA-based analysis does not account for multiple layers of post-transcriptional regulation that are active in microglia.…”

Section: Discussionmentioning

confidence: 99%

High-resolution and differential analysis of rat microglial markers in traumatic brain injury: conventional flow cytometric and bioinformatics analysis

Furman

Gottlieb

Prabhakara

et al. 2020

Sci Rep

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Traumatic brain injury (TBI) results in a cascade of cellular responses, which produce neuroinflammation, partly due to microglial activation. Transforming from surveying to primed phenotypes, microglia undergo considerable molecular changes. However, specific microglial profiles in rat remain elusive due to tedious methodology and limited availability of reagents. Here, we present a flow cytometry-based analysis of rat microglia 24 h after TBI using the controlled cortical impact model, validated with a bioinformatics approach. Isolated microglia are analyzed for morphological changes and their expression of activation markers using flow cytometry, traditional gating-based analysis methods and support the data by employing bioinformatics statistical tools. We use CD45, CD11b/c, and p2y12 receptor to identify microglia and evaluate their activation state using CD32, CD86, RT1B, CD200R, and CD163. The results from logic-gated flow cytometry analysis was validated with bioinformatics-based analysis and machine learning algorithms to detect quantitative changes in morphology and marker expression in microglia due to activation following TBI. Traumatic brain injury (TBI) is attributed to a third of all injury-related deaths in the United States 1. Each year, 1.7 million people receive treatment for brain trauma, and more than 5 million people receive treatment for TBI-related complications and disabilities. TBI can occur in a variety of circumstances and a range of severity levels, which lead to cognitive and behavioral changes and increased risk for acquired neurodegenerative diseases (e.g., Alzheimer's disease or Parkinson's disease) 2-5. Regardless of the severity of the damage caused to the brain tissue, a secondary sub-acute injury mechanism follows the initial injury involving the activation of resident microglia and infiltrating immune cells (such as neutrophils, monocytes, macrophages, lymphocytes etc.) that further contribute to neuroinflammation 6,7. Similarities between microglia and macrophages complicate research, and may often result in considering macrophages and microglia a uniform unit that acts in response to inflammatory stimuli 8,9. Methods for isolation of macrophages from non-CNS tissues are well established and as a result, macrophages are highly investigated. Despite sharing some functional activities with macrophages, it is not accurate to assume that microglia act in the same manner 10. Microglia play a crucial role in both healthy and injured brains. They are constantly active and survey the brain for signals, often acting to remove cellular debris 11. In normal conditions, microglia retain their ramified phenotype. Microglia activation occurs within minutes of injury or infection, resulting in a rapid change in gene expression. Activated microglia undergo dramatic morphological transformation 7 , which is required for their revised role in the neuroinflammatory response. Their newly acquired amoeboid shape makes them indistinguishable from the recruited blood derived macrophages responding...

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Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans

Cited by 57 publications

References 42 publications

The Complexity of Microglial Interactions With Innate and Adaptive Immune Cells in Alzheimer’s Disease

The Complexity of Microglial Interactions With Innate and Adaptive Immune Cells in Alzheimer’s Disease

Microglial/Macrophage polarization and function in brain injury and repair after stroke

High-resolution and differential analysis of rat microglial markers in traumatic brain injury: conventional flow cytometric and bioinformatics analysis

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