The ischemic environment drives microglia and macrophage function.
Stefano Fumagalli,Stefano Fumagalli,Carlo Perego,Francesca Pischiutta,Elisa R. Zanier,Maria Grazia De Simoni +5 more
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TLDR
The selective responses of microglia and macrophages to hypoxia after stroke are discussed and relevant markers are reviewed with the aim of defining the different subpopulations of myeloid cells that are recruited to the injured site.Abstract:
Cells of myeloid origin, such as microglia and macrophages, act at the crossroads of several inflammatory mechanisms during pathophysiology. Besides pro-inflammatory activity (M1 polarization), myeloid cells acquire protective functions (M2) and participate in the neuroprotective innate mechanisms after brain injury. Experimental research is making considerable efforts to understand the rules that regulate the balance between toxic and protective brain innate immunity. Environmental changes affect microglia/macrophage functions. Hypoxia can affect myeloid cell distribution, activity, and phenotype. With their intrinsic differences, microglia and macrophages respond differently to hypoxia, the former depending on ATP to activate and the latter switching to anaerobic metabolism and adapting to hypoxia. Myeloid cell functions include homeostasis control, damage-sensing activity, chemotaxis, and phagocytosis, all distinctive features of these cells. Specific markers and morphologies enable to recognize each functional state. To ensure homeostasis and activate when needed, microglia/macrophage physiology is finely tuned. Microglia are controlled by several neuron-derived components, including contact-dependent inhibitory signals and soluble molecules. Changes in this control can cause chronic activation or priming with specific functional consequences. Strategies, such as stem cell treatment, may enhance microglia protective polarization. This review presents data from the literature that has greatly advanced our understanding of myeloid cell action in brain injury. We discuss the selective responses of microglia and macrophages to hypoxia after stroke and review relevant markers with the aim of defining the different subpopulations of myeloid cells that are recruited to the injured site. We also cover the functional consequences of chronically active microglia and review pivotal works on microglia regulation that offer new therapeutic possibilities for acute brain injury.read more
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Microglia in Physiology and Disease
TL;DR: The diversity of microglia phenotypes and their responses in health, aging, and disease are described and treatment options that modulate microglial phenotypes are discussed.
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Modulators of microglial activation and polarization after intracerebral haemorrhage.
TL;DR: Key studies on modulators of microglial activation and polarization after ICH are summarized, including M1-like and M2-like microglia phenotype markers, transcription factors and key signalling pathways, and the evidence that therapeutic approaches aimed at modulating microglian function might mitigate ICH injury and improve brain repair is presented.
Journal ArticleDOI
Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke
TL;DR: This review summarizes recent progress concerning the mechanisms involved in brain damage, repair and regeneration related to microglia/macrophage activation and phenotype transition after stroke and argues that future translational studies should be targeting multiple key regulating molecules to improve brain repair.
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The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration.
TL;DR: New potential therapeutics need to interfere with these diabetic complications even before changes in the retina are diagnosed, to prevent neuronal apoptosis and blindness in patients.
Journal ArticleDOI
Inflammatory Disequilibrium in Stroke
TL;DR: The frontiers of current knowledge of innate and adaptive immune responses in the brain and how these responses together shape the course of ischemic stroke are explored.
References
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Toby Lawrence,Gioacchino Natoli +1 more
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The Science of Stroke: Mechanisms in Search of Treatments
TL;DR: This review focuses on mechanisms and emerging concepts that drive the science of stroke in a therapeutic direction and poses a number of fundamental questions that may generate new directions for research and possibly new treatments that could reduce the impact of this enormous economic and societal burden.