Cited by 1,748Neuroinflammation and Neurodegeneration MechanismsImmune cells in cancerMultiple Sclerosis Research Studies

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Neuroinflammation and M2 microglia: the good, the bad, and the inflamed

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Cherry, Jonathan D, Olschowka, John A, O’Banion, M Kerry·2014·Journal of Neuroinflammation

DOI 10.1186/1742-2094-11-98PMC PMC4060849

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Abstract

The concept of multiple macrophage activation states is not new. However, extending this idea to resident tissue macrophages, like microglia, has gained increased interest in recent years. Unfortunately, the research on peripheral macrophage polarization does not necessarily translate accurately to their central nervous system (CNS) counterparts. Even though pro- and anti-inflammatory cytokines can polarize microglia to distinct activation states, the specific functions of these states is still an area of intense debate. This review examines the multiple possible activation states microglia can be polarized to. This is followed by a detailed description of microglial polarization and the functional relevance of this process in both acute and chronic CNS disease models described in the literature. Particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.

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Figure 1 Working model of microglial polarization. (A) A variety of cytokines are able to polarize microglia to unique phenotypes. These phenotypes constitute a spectrum as opposed to two binary states. Depending on the stimulus, microglia can be polarized towards one end of the spectrum and be more M1- or M2-like. (B) Upon prolonged or chronic inflammation, an overabundance of inflammatory cytokines skews microglial polarization towards the M1 phenotype. M1 microglia, in turn, produce additional inflammatory cytokines, generating a cycle that further induces inflammation and maintains the M1 state. This skewed population of M1 microglia exhibits impaired phagocytosis and is cytotoxic in, for example, Alzheimer’s disease and multiple sclerosis. (C) To treat neuroinflammatory diseases, certain therapeutic agents, such as glatiramer acetate, bexarotene, and PPARγ agonists, have been used. These treatments have been shown to inhibit inflammation as well as induce M2 activation, resulting in reduced disease severity. A more complete list of such therapeutic agents can be found in Table 2. AD, Alzheimer’s disease, EAE, experimental autoimmune encephalomyelitis; GA, glatiramer acetate; MS, multiple sclerosis.CC BY · PubMed Central

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2 retracted

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Authors: Cherry, J. D., Olschowka, J. A., & O’Banion, M. K.
Affiliations: University of Rochester Medicine (US)
Corresponding author: O’Banion, M Kerry
ORCID: Cherry, Jonathan D
Olschowka, John A
O’Banion, M Kerry
Venue: Journal of Neuroinflammation
Publisher: Springer Science and Business Media LLC
Published: 2014-06-03
Volume: 11
Issue: 1
Pages: 98-98
ISSN: 1742-2094 (ISSN-L)
DOI: 10.1186/1742-2094-11-98
PMC: PMC4060849
OpenAlex: W2147180300
Cited by: 1,748
References: 167
Citations by year: 2026: 127 · 2025: 129 · 2024: 170 · 2023: 157 · 2022: 205 · 2021: 185 · 2020: 173 · 2019: 138 · 2018: 129 · 2017: 128 · 2016: 115 · 2015: 75 · 2014: 14
FWCI: 8.81
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Journal of Neuroinflammation (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Aeronautics and Space Administration (NNX13AC33G)
National Institutes of Health
National Institute on Aging (R01AG030149)
National Institute of Allergy and Infectious Diseases (U19AI091036)
National Institute of Environmental Health Sciences (R01 ES020322)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
Keywords: microglia, M2 microglia, microglial polarization, neuroinflammation, central nervous system disorders, pro- and anti-inflammatory cytokines
MeSH terms: Animals, Central Nervous System, Encephalitis, Humans, Macrophage Activation, Microglia

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Neuroinflammation and M2 microglia: the good, the bad, and the inflamed

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