Evidence map›Paper›PMID 22393433›Full record

ArticlePloS one2012

An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model.

Amutha Selvamani, Pratheesh Sathyan, Rajesh C Miranda, Farida Sohrabji

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 2 pooled it
8.6field-weighted citation impact, top 2% 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

129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 214 citations in OpenAlex.

  1. Pooled it
  2. Systematic review: Association between circulating microRNA expression & stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Pooled it
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  9. The aging ovary impairs acute stroke outcomes.Journal of neuroinflammation · 2023
    Article
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  12. Article
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69 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

4 authors at 2 institutions in 2 countries.

Amutha SelvamaniNeuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of Medicine, College Station, Texas, United States of America.
Pratheesh Sathyan
Rajesh C Miranda
Farida Sohrabji
Texas A&M Health Science Center · USCharité - Universitätsmedizin Berlin · DE

Funding

Impact of Endocrine Aging on Brain and Immune ResponsesR01AG027684 · NIA · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI SOHRABJI, FARIDA · 2006 to 2010
$1.0M
Impact on Reproductive Aging on Neural-Immune ResponsesR01AG028303 · NIA · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI SOHRABJI, FARIDA · 2006 to 2009
$684k
NIA NIH HHS AG027684NIA NIH HHS AG028303NIA NIH HHS R01 AG027684NIA NIH HHS R01 AG028303
6 · The paper itself

Abstract

We previously showed that middle-aged female rats sustain a larger infarct following experimental stroke as compared to younger female rats, and paradoxically, estrogen treatment to the older group is neurotoxic. Plasma and brain insulin-like growth factor-1 (IGF-1) levels decrease with age. However, IGF-1 infusion following stroke, prevents estrogen neurotoxicity in middle-aged female rats. IGF1 is neuroprotective and well tolerated, but also has potentially undesirable side effects. We hypothesized that microRNAs (miRNAs) that target the IGF-1 signaling family for translation repression could be alternatively suppressed to promote IGF-1-like neuroprotection. Here, we report that two conserved IGF pathway regulatory microRNAs, Let7f and miR1, can be inhibited to mimic and even extend the neuroprotection afforded by IGF-1. Anti-mir1 treatment, as late as 4 hours following ischemia, significantly reduced cortical infarct volume in adult female rats, while anti-Let7 robustly reduced both cortical and striatal infarcts, and preserved sensorimotor function and interhemispheric neural integration. No neuroprotection was observed in animals treated with a brain specific miRNA unrelated to IGF-1 (anti-miR124). Remarkably, anti-Let7f was only effective in intact females but not males or ovariectomized females indicating that the gonadal steroid environment critically modifies miRNA action. Let7f is preferentially expressed in microglia in the ischemic hemisphere and confirmed in ex vivo cultures of microglia obtained from the cortex. While IGF-1 was undetectable in microglia harvested from the non-ischemic hemisphere, IGF-1 was expressed by microglia obtained from the ischemic cortex and was further elevated by anti-Let7f treatment. Collectively these data support a novel miRNA-based therapeutic strategy for neuroprotection following stroke.

Indexed as

AnimalsBehavior, AnimalDisease Models, AnimalFemaleGene Expression RegulationInsulin-Like Growth Factor IIschemiaMaleMicrogliaMicroRNAsNeuroprotective AgentsRatsReperfusion InjurySex FactorsStrokeInsulin-Like Growth Factor IMicroRNAsMIRN1 microRNA, ratMIRNLET7 microRNA, ratNeuroprotective Agents

Identifiers

PMID22393433
PMCPMC3290559
OpenAlexW2071432376

What OpenQuestion holds

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LicenceCC BY
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.