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
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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The biochemical basis of neurodegenerative disease: The role of immunoexcitoxicity and ways to possibly attenuate it
TL;DR: In this paper , the authors tried to explain the connection between immune activation and excitotoxicity in central nervous system (CNS) tissues and possible ways to reduce or even stop the reaction.
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Candidate neuroinflammatory markers of cerebral autoregulation dysfunction in human acute brain injury
TL;DR: In this paper , the authors discuss candidate vascular and endothelial markers and what is known about their link to disturbance of the CBF and autoregulation and hypothesise that disturbances to the cerebral vasculature can affect the regulation of CBF, and hence the vascular inflammatory pathways could be a putative mechanism that causes CA dysfunction.
Journal ArticleDOI
Secondary White Matter Injury Mediated by Neuroinflammation after Intracerebral Hemorrhage and Promising Therapeutic Strategies of Targeting the NLRP3 Inflammasome
Weixin Wang,Koichi Hashiguchi +1 more
TL;DR: In this paper , the pyrin domain-containing 3 (NLRP3) inflammasome activation has been shown to exacerbate neuroinflammation and brain injury after intracerebral hemorrhage.
Posted ContentDOI
Reducing the Amount of M1 Microglia by Inhibiting CXCR4 and iNOS Exerts Neuroprotection in a Rat Model of Subarachnoid Hemorrhage
TL;DR: Data indicate that inhibiting CXCR4 and iNOS following SAH produces cerebral protection, and its anti-inflammation provides a potential therapeutic target for treating SAH.
Book ChapterDOI
Neuroprotection Following Stroke
TL;DR: In this paper , the authors present a review of failed clinical trials for the processes involved in the "ischemic cascade", including excitotoxicity, oxidative stress and inflammation, and assess the benefits of these promising strategies.
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