Evidence map›Paper›PMID 26470014›Full record

ArticleGlia2016

Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge.

Diana M Norden, Paige J Trojanowski, Emmanuel Villanueva, Elisa Navarro, Jonathan P Godbout

Abstract read
In one paragraph

Article in Glia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 323 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
323citing papers in PubMed, 4 pooled it
14.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

323 citing papers in PubMed, 4 syntheses or guidelines pooled it, 577 citations in OpenAlex.

  1. Pooled it
  2. The Effects of Cannabinoids on Ischemic Stroke-Associated Neuroinflammation: A Systematic Review.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Pooled it
  3. Pooled it
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  5. Article
  6. Review
  7. Article
  8. Palmitic Acid Amplifies Microglial Inflammatory Activation Involving C5aR1-Sensitive Inflammatory Signaling and JMJD3/H3K27me3-Related Epigenetic Changes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Article
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  12. Article
  13. Prolonged systemic inflammation worsens impairments to astrocyte CaAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  14. Review
  15. Article
  16. Sex influences on tumor innervation.Biology of sex differences · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Article

263 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Diana M NordenDepartment of Neuroscience, The Ohio State University, Columbus, Ohio.
Paige J TrojanowskiDepartment of Neuroscience, The Ohio State University, Columbus, Ohio.
Emmanuel VillanuevaDepartment of Neuroscience, The Ohio State University, Columbus, Ohio.
Elisa NavarroDepartment of Neuroscience, The Ohio State University, Columbus, Ohio.
Jonathan P GodboutDepartment of Neuroscience, The Ohio State University, Columbus, Ohio.
The Ohio State University · US

Funding

Aging, Microglial Dysregulation and DepressionR01AG033028 · NIA · OHIO STATE UNIVERSITY · PI GODBOUT, JONATHAN P · 2009 to 2013
$1.5M
NIA NIH HHS R01 AG033028NIA NIH HHS R01-AG-033028
6 · The paper itself

Abstract

Activation of the peripheral immune system elicits a coordinated response from the central nervous system. Key to this immune to brain communication is that glia, microglia, and astrocytes, interpret and propagate inflammatory signals in the brain that influence physiological and behavioral responses. One issue in glial biology is that morphological analysis alone is used to report on glial activation state. Therefore, our objective was to compare behavioral responses after in vivo immune (lipopolysaccharide, LPS) challenge to glial specific mRNA and morphological profiles. Here, LPS challenge induced an immediate but transient sickness response with decreased locomotion and social interaction. Corresponding with active sickness behavior (2-12 h), inflammatory cytokine mRNA expression was elevated in enriched microglia and astrocytes. Although proinflammatory cytokine expression in microglia peaked 2-4 h after LPS, astrocyte cytokine, and chemokine induction was delayed and peaked at 12 h. Morphological alterations in microglia (Iba-1(+)) and astrocytes (GFAP(+)), however, were undetected during this 2-12 h timeframe. Increased Iba-1 immunoreactivity and de-ramified microglia were evident 24 and 48 h after LPS but corresponded to the resolution phase of activation. Morphological alterations in astrocytes were undetected after LPS. Additionally, glial cytokine expression did not correlate with morphology after four repeated LPS injections. In fact, repeated LPS challenge was associated with immune and behavioral tolerance and a less inflammatory microglial profile compared with acute LPS challenge. Overall, induction of glial cytokine expression was sequential, aligned with active sickness behavior, and preceded increased Iba-1 or GFAP immunoreactivity after LPS challenge.

Indexed as

AnimalsAstrocytesBrainCalcium-Binding ProteinsCytokinesDisease Models, AnimalExploratory BehaviorGlial Fibrillary Acidic ProteinInflammationLipopolysaccharidesMice, Inbred BALB CMicrofilament ProteinsMicrogliaMotor ActivityRNA, MessengerAif1 protein, mouseCalcium-Binding ProteinsCytokinesGlial Fibrillary Acidic Proteinglial fibrillary astrocytic protein, mouseLipopolysaccharidesMicrofilament ProteinsRNA, Messengerastrocyteslipopolysaccharidemicroglianeuroinflammationsickness behavior

Identifiers

PMID26470014
PMCPMC4707977
OpenAlexW1915977580

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.