The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke
Open accessAbstract
The immune response to ischemic stroke is an area of study that is at the forefront of stroke research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, the innate immune system is activated by danger-associated molecular signals from stressed and dying neurons. Microglia, an immune cell population within the central nervous system which phagocytose cell debris and modulate the immune response via cytokine signaling, are the first cell population to become activated. Soon after, monocytes arrive from the peripheral immune system, differentiate into macrophages, and further aid in the immune response. Upon activation, both microglia and monocyte-derived macrophages are capable of polarizing into phenotypes which can either promote or attenuate the inflammatory response. Phenotypes which promote the inflammatory response are hypothesized to increase neuronal damage and impair recovery of neuronal function during the later phases of ischemic stroke. Therefore, modulating neuroimmune cells to adopt an anti-inflammatory response post ischemic stroke is an area of current research interest and potential treatment development. In this review, we outline the biology of microglia and monocyte-derived macrophages, further explain their roles in the acute, subacute, and chronic stages of ischemic stroke, and highlight current treatment development efforts which target these cells in the context of ischemic stroke.
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Monocyte-derived brain macrophages have been reported earlier, but these studies were largely focused on conditions of experimental challenge.
“Monocyte-derived brain M F have been reported earlier, but these studies were largely focused on conditions of experimental challenge 20-25,59 .”
From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [25]
The Introduction’s ‘Immune Response to Stroke’ section describes monocyte-derived macrophages entering the brain after ischemic injury, and ‘Background: Monocyte-Derived Macrophages’ cites their identification in an infarcted brain (page numbers unavailable). These support earlier reports under experimental challenge, but the paper does not establish that earlier studies were largely confined to such conditions. (LLM, conf=0.78)
Experimental — accuracy not yet measuredMonocyte and monocyte-derived macrophage contributions to brain pathologies are well documented in various animal models and human disorders.
“Involvement of these cells has been shown in the development, progression and resolution of experimental autoimmune encephalitis (EAE) 20-22 , stroke 23,24 , Alzheimer's disease 25,26 and viral encephalitis 27 .”
From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [25]
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- Authors
- Wicks, E. E., Ran, K. R., Kim, J. E., Xu, R., Lee, R. P., & Jackson, C. M.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Jackson, Christopher M.
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2022-06-20
- Volume
- 13
- Pages
- 897022-897022
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC9251541
- OpenAlex
- W4283216970
- Cited by
- 92
- References
- 184
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 24 · 2023: 21 · 2022: 2
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Sarnoff Cardiovascular Research Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- ischemic stroke, microglia, monocyte-derived macrophages, neuroinflammation, innate immune response, cerebral ischemia, monocyte differentiation, macrophage polarization, anti-inflammatory therapy, neuronal injury
- MeSH terms
- Ischemic Stroke, Humans, Macrophages, Phagocytosis, Microglia, Stroke
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