Evidence map›Paper›PMID 24723305›Full record

ArticleGlia2014

Spreading depression requires microglia and is decreased by their M2a polarization from environmental enrichment.

Kae M Pusic, Aya D Pusic, Jordan Kemme, Richard P Kraig

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 2 pooled it
5.8field-weighted citation impact, top 4% 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

51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.

  1. Pooled it
  2. Imaging the inflammatory phenotype in migraine.The journal of headache and pain · 2022
    Pooled it
  3. Review
  4. Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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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

4 authors at 1 institution in 1 country.

Kae M PusicDepartment of Neurology, The University of Chicago, Chicago, Illinois.
Aya D Pusic
Jordan Kemme
Richard P Kraig
University of Chicago · US

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
THE MOLECULAR BASIS OF B-MANNOSIDOSISP01HD009402 · NICHD · UNIVERSITY OF CHICAGO · PI KRAIG, RICHARD P · 1985 to 2015
$13.0M
HYDROGEN IONS AND BRAIN INFARCTIONR01NS019108 · NINDS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI KRAIG, RICHARD P · 1985 to 2019
$5.2M
Exosome RNA-Therapeutics to Promote CNS MyelinationUH2TR000918 · NCATS · UNIVERSITY OF CHICAGO · PI KRAIG, RICHARD P · 2013 to 2014
$568k
NCATS NIH HHS 1-UH2 TR000918NCATS NIH HHS UH2 TR000918NCATS NIH HHS UL1 TR000430NICHD NIH HHS 5 PO1 HD 09402NICHD NIH HHS P01 HD009402NINDS NIH HHS NS-19108NINDS NIH HHS R01 NS019108
6 · The paper itself

Abstract

Microglia play an important role in fine-tuning neuronal activity. In part, this involves their production of tumor necrosis factor-alpha (TNFα), which increases neuronal excitability. Excessive synaptic activity is necessary to initiate spreading depression (SD). Increased microglial production of proinflammatory cytokines promotes initiation of SD, which, when recurrent, may play a role in conversion of episodic to high frequency and chronic migraine. Previous work shows that this potentiation of SD occurs through increased microglial production of TNFα and reactive oxygen species, both of which are associated with an M1-skewed microglial population. Hence, we explored the role of microglia and their M1 polarization in SD initiation. Selective ablation of microglia from rat hippocampal slice cultures confirmed that microglia are essential for initiation of SD. Application of minocycline to dampen M1 signaling led to increased SD threshold. In addition, we found that SD threshold was increased in rats exposed to environmental enrichment. These rats had increased neocortical levels of interleukin-11 (IL-11), which decreases TNFα signaling and polarized microglia to an M2a-dominant phenotype. M2a microglia reduce proinflammatory signaling and increase production of anti-inflammatory cytokines, and therefore may protect against SD. Nasal administration of IL-11 to mimic effects of environmental enrichment likewise increased M2a polarization and increased SD threshold, an effect also seen in vitro. Similarly, application of conditioned medium from M2a polarized primary microglia to slice cultures also increased SD threshold. Thus, microglia and their polarization state play an essential role in SD initiation, and perhaps by extension migraine with aura and migraine.

Indexed as

EnvironmentSignal TransductionAnimalsCells, CulturedCentral Nervous System AgentsCytokinesHippocampusHousing, AnimalInterleukin-11MaleMembrane PotentialsMicroelectrodesMicrogliaMinocyclineNeocortexOxidative StressCentral Nervous System AgentsCytokinesInterleukin-11MinocyclineTumor Necrosis Factor-alphaenvironmental enrichmenthippocampal slice cultureinterleukin-11microglial polarizationmigraine

Identifiers

PMID24723305
PMCPMC4081540
OpenAlexW2133108518

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.