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Journal ArticleDOI

Review: Activation patterns of microglia and their identification in the human brain

TLDR
The question as to what extent different activation states of microglia exist in the human central nervous system is discussed, which tools can be used to identify them and emerging evidence for such changes in ageing and in Alzheimer's disease is discussed.
Abstract
Microglia in the central nervous system are usually maintained in a quiescent state. When activated, they can perform many diverse functions which may be either beneficial or harmful depending on the situation. Although microglial activation may be accompanied by changes in morphology, morphological changes cannot accurately predict the function being undertaken by a microglial cell. Studies of peripheral macrophages and in vitro and animal studies of microglia have resulted in the definition of specific activation states: M1 (classical activation) and M2 (sometimes subdivided into alternative activation and acquired deactivation). Some authors have suggested that these might be an overlapping continuum of functions rather than discrete categories. In this review, we consider translational aspects of our knowledge of microglia: specifically, we discuss the question as to what extent different activation states of microglia exist in the human central nervous system, which tools can be used to identify them and emerging evidence for such changes in ageing and in Alzheimer's disease.

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Reactive Astrocytes: Production, Function, and Therapeutic Potential

TL;DR: Recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful are summarized.
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Neuroinflammation and M2 microglia: the good, the bad, and the inflamed.

TL;DR: The multiple possible activation states microglia can be polarized to are examined and particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.
Journal ArticleDOI

Microglial M1/M2 polarization and metabolic states.

TL;DR: The polarization states of microglia and their relationship to mitochondrial metabolism are examined and a role of metabolic reprogramming in the regulation of the innate inflammatory response is suggested.
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Microglial and Macrophage polarization—new Prospects for Brain Repair

TL;DR: It is argued that therapeutic approaches targeting cerebral inflammation should shift from broad suppression of microglia and macrophages towards subtle adjustment of the balance between their phenotypes, and breakthroughs in the identification of regulatory molecules that control these phenotypic shifts could ultimately accelerate research towards curing brain disorders.
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Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease.

TL;DR: The mechanisms and important role of pro-inflammatory cytokines in the pathogenesis of AD, and the ongoing drug targeting pro- inflammatory cytokine for therapeutic modulation are discussed.
References
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Journal ArticleDOI

Exploring the full spectrum of macrophage activation.

TL;DR: This Review suggests a new grouping of macrophages based on three different homeostatic activities — host defence, wound healing and immune regulation, and proposes that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation.
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Alternative activation of macrophages

TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
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Monocyte and macrophage heterogeneity

TL;DR: Recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues.
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Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo

TL;DR: Using in vivo two-photon imaging in neocortex, it is found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions.
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Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages

TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
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