Cited by 422Neuroinflammation and Neurodegeneration MechanismsInflammasome and immune disordersTraumatic Brain Injury and Neurovascular Disturbances

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Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease

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Norden, Diana M., Muccigrosso, Megan M., Godbout, Jonathan P.·2015·Neuropharmacology

DOI 10.1016/j.neuropharm.2014.10.028PMC PMC4430467

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Abstract

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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Additional file 11 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768066
Additional file 6 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768093
Additional file 13 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768072
Additional file 14 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768075
Additional file 8 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768099
Additional file 10 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768063
Additional file 9 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768102
Additional file 7 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768096
Additional file 5 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768090
Additional file 12 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768069
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Additional file 3 of Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury
Xiong, W., Li, C., Kong, G., Zeng, Q., Wang, S., Yin, G., Gu, J., & Fan, J. (2024) · Figshare · doi:10.6084/m9.figshare.26553983
Additional file 2 of Whole blood stimulation provides preliminary evidence of altered immune function following SRC
Battista, A. P. D., Rhind, S. G., Shiu, M. Y., & Hutchison, M. G. (2024) · Figshare · doi:10.6084/m9.figshare.24995612
Additional file 1 of Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury
Xiong, W., Li, C., Kong, G., Zeng, Q., Wang, S., Yin, G., Gu, J., & Fan, J. (2024) · Figshare · doi:10.6084/m9.figshare.26553950
Additional file 1 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768078
Additional file 4 of Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury
Xiong, W., Li, C., Kong, G., Zeng, Q., Wang, S., Yin, G., Gu, J., & Fan, J. (2024) · Figshare · doi:10.6084/m9.figshare.26553989
Additional file 2 of Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury
Xiong, W., Li, C., Kong, G., Zeng, Q., Wang, S., Yin, G., Gu, J., & Fan, J. (2024) · Figshare · doi:10.6084/m9.figshare.26553965
Additional file 2 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768081
Additional file 3 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768084
Additional file 1 of Whole blood stimulation provides preliminary evidence of altered immune function following SRC
Battista, A. P. D., Rhind, S. G., Shiu, M. Y., & Hutchison, M. G. (2024) · Figshare · doi:10.6084/m9.figshare.24995519
Additional file 4 of Epigenetic regulation of innate immune memory in microglia
Zhang, X., Kracht, L., Lerário, A. M., Dubbelaar, M. L., Brouwer, N., Wesseling, E. M., Boddeke, E., Eggen, B. J. L., & Kooistra, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19768087
Additional file 3 of Whole blood stimulation provides preliminary evidence of altered immune function following SRC
Battista, A. P. D., Rhind, S. G., Shiu, M. Y., & Hutchison, M. G. (2024) · Figshare · doi:10.6084/m9.figshare.26667574
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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)
DOI: 10.1016/j.neuropharm.2014.10.028
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease

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