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Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease
Open accessAbstract
Glia of the central nervous system (CNS) help to maintain homeostasis in the brain and support efficient neuronal function. Microglia are innate immune cells of the brain that mediate responses to pathogens and injury. They have key roles in phagocytic clearing, surveying the local microenvironment and propagating inflammatory signals. An interruption in homeostasis induces a cascade of conserved adaptive responses in glia. This response involves biochemical, physiological and morphological changes and is associated with the production of cytokines and secondary mediators that influence synaptic plasticity, cognition and behavior. This reorganization of host priorities represents a beneficial response that is normally adaptive but may become maladaptive when the profile of microglia is compromised. For instance, microglia can develop a primed or pro-inflammatory mRNA, protein and morphological profile with aging, traumatic brain injury and neurodegenerative disease. As a result, primed microglia exhibit an exaggerated inflammatory response to secondary and sub-threshold challenges. Consequences of exaggerated inflammatory responses by microglia include the development of cognitive deficits, impaired synaptic plasticity and accelerated neurodegeneration. Moreover, impairments in regulatory systems in these circumstances may make microglia more resistant to negative feedback and important functions of glia can become compromised and dysfunctional. Overall, the purpose of this review is to discuss key concepts of microglial priming and immune-reactivity in the context of aging, traumatic CNS injury and neurodegenerative disease. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.
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“A primed microglia profile includes (1) increased basal expression of inflammatory markers and mediators, (2) decreased activation threshold to express and release pro-inflammatory molecules, and (3) exaggerated inflammatory response to immune challenge (93).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [93]
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Metadata
- Authors
- Norden, D. M., Muccigrosso, M. M., & Godbout, J. P.
- Affiliations
- The Ohio State University (US)
- The Ohio State University Wexner Medical Center (US)
- Corresponding author
- Godbout, Jonathan P.
- ORCID
- Godbout, Jonathan P.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 96
- Issue
- Pt A
- Pages
- 29-41
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC4430467
- OpenAlex
- W2051504363
- Cited by
- 413
- References
- 156
- Citations by year
- 2026: 37 · 2025: 36 · 2024: 28 · 2023: 31 · 2022: 37 · 2021: 44 · 2020: 41 · 2019: 33 · 2018: 41 · 2017: 34 · 2016: 29 · 2015: 21
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01-AG-033028)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- microglial priming, microglial activation, aging, traumatic brain injury, neurodegenerative diseases, neuroinflammation, secondary injury, cognitive impairment, synaptic plasticity, neurodegeneration, innate immunity, neuroimmunology
- MeSH terms
- Aging, Astrocytes, Brain Injuries, Encephalitis, Craniocerebral Trauma, Humans, Male, Neuronal Plasticity, Microglia, Inflammation Mediators, Neurodegenerative Diseases, Illness Behavior
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