Evidence map›Paper›PMID 29866755›Full record

ArticleStroke2018

Inhibition of miR-141-3p Ameliorates the Negative Effects of Poststroke Social Isolation in Aged Mice.

Rajkumar Verma, Rodney M Ritzel, Nia M Harris, Juneyoung Lee, TaeHee Kim, Gopal Pandi, Raghu Vemuganti, Louise D McCullough

Abstract read
In one paragraph

Article in Stroke, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

32 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  14. CD11bJournal of immunology (Baltimore, Md. : 1950) · 2022
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  19. Noncoding RNA crosstalk in brain health and diseases.Neurochemistry international · 2021
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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

8 authors.

Rajkumar VermaFrom the Department of Neuroscience, UConn Health, Farmington, CT (R.V., R.M.R., N.M.H., L.D.M.).
Rodney M RitzelFrom the Department of Neuroscience, UConn Health, Farmington, CT (R.V., R.M.R., N.M.H., L.D.M.).
Nia M HarrisFrom the Department of Neuroscience, UConn Health, Farmington, CT (R.V., R.M.R., N.M.H., L.D.M.).
Juneyoung LeeDepartment of Neurology, McGovern Medical School University of Texas Health Science Center, Houston (J.L., L.D.M.).
TaeHee KimDepartment of Neurological Surgery, University of Wisconsin, Madison (T.K., G.P., R.V.).
Gopal PandiDepartment of Neurological Surgery, University of Wisconsin, Madison (T.K., G.P., R.V.).
Raghu VemugantiDepartment of Neurological Surgery, University of Wisconsin, Madison (T.K., G.P., R.V.).
Louise D McCulloughFrom the Department of Neuroscience, UConn Health, Farmington, CT (R.V., R.M.R., N.M.H., L.D.M.) Louise.D.McCullough@uth.tmc.edu.

Funding

Pyschosocial Stress and the Response to StrokeR37NS096493 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCCULLOUGH, LOUISE D. · 2016 to 2022
$5.2M
Psychosocial Stress and Behavioral Response to StrokeR01NS077769 · NINDS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI MCCULLOUGH, LOUISE D. · 2011 to 2014
$2.3M
Therapeutic Targeting of an lncRNA in Experimental Stroke Using STAIR CriteriaR01NS099531 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI VEMUGANTI, RAGHU · 2017 to 2021
$2.0M
Targeting alpha-synuclein after cerebral ischemia as a function of sex and ageR01NS101960 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI VEMUGANTI, RAGHU · 2017 to 2021
$1.6M
NINDS NIH HHS R01 NS077769NINDS NIH HHS R01 NS099531NINDS NIH HHS R01 NS101960NINDS NIH HHS R37 NS096493
6 · The paper itself

Abstract

background and purposeSocial isolation increases mortality and impairs recovery after stroke in clinical populations. These detrimental effects have been recapitulated in animal models, although the exact mechanism mediating these effects remains unclear. Dysregulation of microRNAs (miRNAs) occurs in both strokes as well as after social isolation, which trigger changes in many downstream genes. We hypothesized that miRNA regulation is involved in the detrimental effects of poststroke social isolation in aged animals.

methodsWe pair-housed 18-month-old C57BL/6 male mice for 2 weeks before a 60-minute right middle cerebral artery occlusion or sham surgery and then randomly assigned mice to isolation or continued pair housing immediately after surgery. We euthanized mice either at 3, 7, or 15 days after surgery and isolated the perilesional frontal cortex for whole microRNAome analysis. In an additional cohort, we treated mice 1 day after stroke onset with an in vivo-ready antagomiR-141 for 3 days.

resultsUsing whole microRNAome analysis of 752 miRNAs, we identified miR-141-3p as a unique miRNA that was significantly upregulated in isolated mice in a time-dependent manner up to 2 weeks after stroke. Posttreatment with an antagomiR-141-3p reduced the postisolation-induced increase in miR-141-3p to levels almost equal to those of pair-housed stroke controls. This treatment significantly reduced mortality (by 21%) and normalized infarct volume and neurological scores in poststroke-isolated mice. Quantitative PCR analysis revealed a significant upregulation of Tgfβr1 (transforming growth factor beta receptor 1, a direct target of miR-141-3p) and Igf-1 (insulin-like growth factor 1) mRNA after treatment with antagomiR. Treatment also increased the expression of other pleiotropic cytokines such as Il-6 (interleukin 6) and Tnf-α (tumor necrosis factor-α), an indirect or secondary target) in brain tissue.

conclusionsmiR-141-3p is increased with poststroke isolation. Inhibition of miR-141-3p improved mortality, neurological deficits, and decreased infarct volumes. Importantly, these therapeutic effects occurred in aged animals, the population most at risk for stroke and poststroke isolation.

Indexed as

AnimalsCytokinesDisease Models, AnimalFrontal LobeMaleMiceMicroRNAsRecovery of FunctionSocial IsolationStrokeCytokinesMicroRNAsMirn141 microRNA, mousecytokineshousingmicroRNAsneuroprotectionsocial isolation

Identifiers

PMID29866755
PMCPMC6019570

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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.