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Cited by 283Traumatic Brain Injury and Neurovascular DisturbancesNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury Research

Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia

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Fenn, Ashley M., Gensel, John C., Huang, Yan, Popovich, Phillip G., Lifshitz, Jonathan, Godbout, Jonathan P.·2014·Biological Psychiatry
DOI 10.1016/j.biopsych.2013.10.014PMC PMC4000292
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Abstract

Background Traumatic brain injury (TBI) is associated with a higher incidence of depression. The majority of individuals who suffer a TBI are juveniles and young adults, and thus, the risk of a lifetime of depressive complications is a significant concern. The etiology of increased TBI-associated depression is unclear but may be inflammatory-related with increased brain sensitivity to secondary inflammatory challenges (e.g., stressors, infection, and injury). Methods Adult male BALB/c mice received a sham (n = 52) or midline fluid percussion injury (TBI; n = 57). Neuroinflammation, motor coordination (rotarod), and depressive behaviors (social withdrawal, immobility in the tail suspension test, and anhedonia) were assessed 4 hours, 24 hours, 72 hours, 7 days, or 30 days later. Moreover, 30 days after surgery, sham and TBI mice received a peripheral injection of saline or lipopolysaccharide (LPS) and microglia activation and behavior were determined. Results Diffuse TBI caused inflammation, peripheral cell recruitment, and microglia activation immediately after injury coinciding with motor coordination deficits. These transient events resolved within 7 days. Nonetheless, 30 days post-TBI a population of deramified and major histocompatibility complex II(+) (primed) microglia were detected. After a peripheral LPS challenge, the inflammatory cytokine response in primed microglia of TBI mice was exaggerated compared with microglia of controls. Furthermore, this LPS-induced microglia reactivity 30 days after TBI was associated with the onset of depressive-like behavior. Conclusions These results implicate a primed and immune-reactive microglial population as a possible triggering mechanism for the development of depressive complications after TBI.

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  • TBI induces a primed microglial phenotype, defined by altered morphology and increased expression of MHC-II and CD68.

    “Recent data demonstrate that TBI induces a primed microglial phenotype, defined by altered morphology and increased expression of MHC-II and CD68 (204, 208).”

    From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [204]

    The Results section on TBI-associated microglia priming reports altered microglial morphology and increased MHC-II expression 30 days after diffuse TBI in mice. The paper does not report increased CD68 after TBI; its Introduction mentions CD68 as a marker in other models of microglial priming. (LLM, conf=0.90)

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References 79 · Cited by 283

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Authors
Fenn, A. M., Gensel, J. C., Huang, Y., Popovich, P. G., Lifshitz, J., & Godbout, J. P.
Affiliations
  • The Ohio State University (US)
  • University of Kentucky (US)
  • Barrow Neurological Institute (US)
Corresponding author
Godbout, Jonathan P.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2014-10
Volume
76
Issue
7
Pages
575-584
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2013.10.014
PMC
PMC4000292
OpenAlex
W2138629438
Cited by
283
References
79
Citations by year
2026: 11 · 2025: 15 · 2024: 28 · 2023: 15 · 2022: 26 · 2021: 28 · 2020: 33 · 2019: 24 · 2018: 32 · 2017: 15 · 2016: 23 · 2015: 21 · 2014: 12
FWCI
11.86
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging Grant (R01-AG-033028)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
traumatic brain injury, depression, microglial activation, neuroinflammation, lipopolysaccharide challenge, depression-like behavior, anhedonia, social withdrawal, motor coordination deficits, MHC class II, fluid percussion injury, peripheral immune activation
MeSH terms
Animals, Brain Injuries, Depression, Encephalitis, Gliosis, Lipopolysaccharides, Male, Mice, Inbred BALB C, Motor Activity, Time Factors, Microglia, Mice

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