Aged lipid‐laden microglia display impaired responses to stroke
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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.
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Many studies have demonstrated a phagocytosis defect associated with LD accumulation in microglia.
“Many studies have demonstrated a phagocytosis defect associated with LD accumulation in microglia (11, 13).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [13]
Excessive lipid droplet accumulation within microglia leads to a decline in their phagocytic activity.
“However, we and others (11, 13, 39) have observed that excessive LD accumulation within microglia led to a decline in their phagocytic activity, potentially reducing the efficiency of Aβ clearance in the AD brain.”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [13]
The initial neuroprotective effect of lipid droplets after injury may gradually become detrimental over time.
“Moreover, the initial neuroprotective effect of LDs after injury may gradually become detrimental over time (13).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [13]
The presence of lipid-laden microglia correlates with an impaired response to stroke in aged mice.
“The presence of these lipid-laden microglia correlates with an impaired response to stroke in aged mice (Arbaizar-Rovirosa et al., 2023).”
From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Arbaizar-Rovirosa et al., 2023
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“Moreover, the initial neuroprotective effect of LDs after injury may gradually become detrimental over time ( 13 ).”
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- Authors
- Arbaizar‐Rovirosa, M., Pedragosa, J., Lozano, J. J., Casal, C., Pol, A., Gallizioli, M., & Planas, A. M.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Planas, Anna M
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2022-12-21
- Volume
- 15
- Issue
- 2
- Pages
- e17175-e17175
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC9906381
- OpenAlex
- W4312066749
- Cited by
- 94
- References
- 22
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 29 · 2023: 16 · 2022: 4
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- EC ¦ European Regional Development Fund
- MEC ¦ Consejo Superior de Investigaciones Científicas
- Ministerio de Ciencia e Innovación (PID2020‐113202RB‐I00, PRE2018‐085737)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- stroke, cerebral ischemia-reperfusion injury, microglial depletion, microglial repopulation, innate immune response, type I interferon, lipid droplet formation, neuroinflammation, functional recovery, motor function, aging
- MeSH terms
- Animals, Brain Ischemia, Ischemia, Lipids, Mice, Inbred C57BL, Microglia, Stroke, Mice
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