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Updated: Sep 21, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
The ischemic environment drives microglia and macrophage function
Stefano Fumagalli1, Carlo Perego2, Francesca Pischiutta2
1Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy ; Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico , Milan , Italy.
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.
Insights
Myeloid cells like microglia and macrophages have distinct roles in brain injury. Understanding their responses to hypoxia and developing strategies to modulate their functions offers new therapeutic avenues for brain repair.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Myeloid cells, including microglia and macrophages, are crucial in brain injury pathophysiology, exhibiting both pro-inflammatory (M1) and neuroprotective (M2) functions.
- Environmental factors, particularly hypoxia, significantly influence myeloid cell distribution, activity, and phenotype, with distinct responses observed between microglia and macrophages.
- The intricate regulation of microglia and macrophage physiology, including neuron-derived inhibitory signals, is vital for maintaining homeostasis and responding appropriately to brain injury.
Purpose of the Study:
- To review and synthesize current literature on myeloid cell involvement in brain injury.
- To elucidate the differential responses of microglia and macrophages to hypoxia following stroke.
- To explore therapeutic strategies targeting myeloid cell polarization for enhanced brain repair.
Main Methods:
- Literature review of experimental research on myeloid cell function in brain injury.
- Analysis of studies investigating the effects of hypoxia on microglia and macrophages.
- Examination of markers and morphologies to identify myeloid cell subpopulations and functional states.
Main Results:
- Microglia and macrophages display unique adaptations to hypoxia, impacting their roles in brain injury.
- Specific markers and morphologies are identified to distinguish functional states of recruited myeloid cells.
- Chronic activation of microglia has significant functional consequences, highlighting the need for precise regulation.
Conclusions:
- Modulating myeloid cell polarization, potentially through strategies like stem cell treatment, holds promise for enhancing neuroprotection after brain injury.
- A deeper understanding of microglia and macrophage regulation provides new therapeutic possibilities for acute brain injury.
- Defining myeloid cell subpopulations recruited to injured sites is critical for targeted interventions.
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