The Semantics of Microglia Activation: Neuroinflammation, Homeostasis, and Stress
Open accessAbstract
Microglia are emerging as critical regulators of neuronal function and behavior in nearly every area of neuroscience. Initial reports focused on classical immune functions of microglia in pathological contexts, however, immunological concepts from these studies have been applied to describe neuro-immune interactions in the absence of disease, injury, or infection. Indeed, terms such as 'microglia activation' or 'neuroinflammation' are used ubiquitously to describe changes in neuro-immune function in disparate contexts; particularly in stress research, where these terms prompt undue comparisons to pathological conditions. This creates a barrier for investigators new to neuro-immunology and ultimately hinders our understanding of stress effects on microglia. As more studies seek to understand the role of microglia in neurobiology and behavior, it is increasingly important to develop standard methods to study and define microglial phenotype and function. In this review, we summarize primary research on the role of microglia in pathological and physiological contexts. Further, we propose a framework to better describe changes in microglia1 phenotype and function in chronic stress. This approach will enable more precise characterization of microglia in different contexts, which should facilitate development of microglia-directed therapeutics in psychiatric and neurological disease.
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Activated microglial cells can exert both neurotoxic and neuroprotective effects depending on the phenotype they acquire upon activation.
“The role of activated microglial cells is crucial in neuroinflammation since they can exert both neurotoxic and neuroprotective effects depending on the phenotype they acquire upon activation (Woodburn et al., 2021).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Woodburn et al., 2021
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“Homeostatic microglia typically have a small circular cell body and ramified processes, whereas in the setting of injury, reactive microglia typically have larger cell bodies with an amoeboid shape and short, thick processes (Woodburn et al. 2021).”
- Authors
- Woodburn, S. C., Bollinger, J. L., & Wohleb, E. S.
- Affiliations
- University of Cincinnati (US)
- Corresponding author
- Wohleb, Eric S.
- Venue
- Journal of Neuroinflammation
- Published
- 2021-11-06
- Volume
- 18
- Issue
- 1
- Pages
- 258-258
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC8571840
- OpenAlex
- W3211761706
- Cited by
- 783
- References
- 261
- Citations by year
- 2026: 138 · 2025: 244 · 2024: 204 · 2023: 142 · 2022: 53 · 2021: 1
- FWCI
- 11.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- foundation for the national institutes of health (R21-MH120614, R01-MH-123545)
- brain and behavior research foundation (NARSAD Young Investigator Grant, 25488)
- college of medicine, university of cincinnati (University of Cincinnati Neurobiology Research Center Pilot Award)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- microglial activation, neuroinflammation, neuroimmune interactions, chronic stress, microglial phenotype, homeostasis, stress-related psychiatric disorders, terminology standardization
- MeSH terms
- Neuroinflammatory Diseases, Animals, Homeostasis, Humans, Terminology as Topic, Semantics, Stress, Physiological, Microglia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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