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Updated: Jun 12, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Aged lipid-laden microglia display impaired responses to stroke
Maria Arbaizar-Rovirosa1,2, Jordi Pedragosa1,2, Juan J Lozano3
1Department of Neuroscience and Experimental Therapeutics, Instituto de Investigaciones Biomédicas de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
Abstract:
Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worse neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor 1 receptor antagonists enables transient microglia depletion that is followed by microglia repopulation after treatment interruption, causing no known harm to mice. We tested whether this strategy restored microglia function and ameliorated stroke outcome in old mice. Cerebral ischemia/reperfusion induced innate immune responses in microglia highlighted by type I interferon and metabolic changes involving lipid droplet biogenesis. Old microglia accumulated lipids under steady state and displayed exacerbated innate immune responses to stroke. Microglia repopulation in old mice reduced lipid-laden microglia, and the cells exhibited reduced inflammatory responses to ischemia. Moreover, old mice with renewed microglia showed improved motor function 2 weeks after stroke. We conclude that lipid deposits in aged microglia impair the cellular responses to ischemia and worsen functional recovery in old mice.
Insights
Aging microglia accumulate lipids, impairing brain repair after stroke. Renewing microglia through targeted depletion and repopulation improved motor function in aged mice, offering a potential therapeutic strategy for stroke recovery.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Microglia, the brain's immune cells, show dysfunction in aged individuals, potentially worsening stroke outcomes.
- Accumulation of lipids in aged microglia contributes to exacerbated inflammatory responses during cerebral ischemia.
Purpose of the Study:
- To investigate if microglia repopulation can restore microglial function and improve stroke outcomes in aged mice.
- To determine the role of lipid accumulation in aged microglia during ischemic stroke.
Main Methods:
- Utilized colony-stimulating factor 1 receptor antagonists for transient microglia depletion and subsequent repopulation in aged mice.
- Induced cerebral ischemia/reperfusion to model stroke and analyzed microglial responses, including lipid droplet biogenesis and inflammatory markers.
- Assessed motor function recovery in aged mice post-stroke following microglia repopulation.
Main Results:
- Microglia repopulation in aged mice reduced lipid-laden microglia and dampened inflammatory responses to ischemia.
- Renewed microglia exhibited normalized metabolic profiles and reduced type I interferon responses.
- Aged mice with repopulated microglia demonstrated significantly improved motor function two weeks after stroke.
Conclusions:
- Lipid deposits in aged microglia impair cellular responses to ischemia and hinder functional recovery.
- Microglia repopulation is a promising strategy to ameliorate stroke outcomes in the elderly by restoring microglial function.
