Evidence map›Paper›PMID 31327315›Full record

ArticleStroke2019

Induction of DNA Hydroxymethylation Protects the Brain After Stroke.

Kahlilia C Morris-Blanco, TaeHee Kim, Mary S Lopez, Mario J Bertogliat, Bharath Chelluboina, Raghu Vemuganti

Open access · bronzeAbstract read
In one paragraph

Article in Stroke, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

31 citing papers in PubMed, 44 citations in OpenAlex.

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  17. Epigenetic mechanisms and potential therapeutic targets in stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Review
  18. The Role of DNA Methylation in Stroke Recovery.International journal of molecular sciences · 2022
    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

6 authors at 2 institutions in 1 country.

Kahlilia C Morris-BlancoFrom the Department of Neurological Surgery (K.C.M.-B., T.K., M.S.L., M.J.B., B.C., R.V.), University of Wisconsin-Madison, Madison, WI.
TaeHee KimFrom the Department of Neurological Surgery (K.C.M.-B., T.K., M.S.L., M.J.B., B.C., R.V.), University of Wisconsin-Madison, Madison, WI.
Mary S LopezFrom the Department of Neurological Surgery (K.C.M.-B., T.K., M.S.L., M.J.B., B.C., R.V.), University of Wisconsin-Madison, Madison, WI.
Mario J BertogliatFrom the Department of Neurological Surgery (K.C.M.-B., T.K., M.S.L., M.J.B., B.C., R.V.), University of Wisconsin-Madison, Madison, WI.
Bharath ChelluboinaFrom the Department of Neurological Surgery (K.C.M.-B., T.K., M.S.L., M.J.B., B.C., R.V.), University of Wisconsin-Madison, Madison, WI.
Raghu VemugantiFrom the Department of Neurological Surgery (K.C.M.-B., T.K., M.S.L., M.J.B., B.C., R.V.), University of Wisconsin-Madison, Madison, WI.
Neurological Surgery · USUniversity of Wisconsin–Madison · US

Funding

DNA hydroxymethylation and post stroke brain damageR01NS109459 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI VEMUGANTI, RAGHU · 2018 to 2022
$2.1M
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
LncRNA FosDT mediates ischemic brain damageR21NS095192 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI VEMUGANTI, RAGHU · 2015 to 2016
$558k
NINDS NIH HHS R01 NS099531NINDS NIH HHS R01 NS101960NINDS NIH HHS R01 NS109459NINDS NIH HHS R21 NS095192
6 · The paper itself

Abstract

Background and Purpose- Epigenetics play a significant role in brain pathologies. We currently evaluated the role of a recently discovered brain-enriched epigenetic modification known as 5-hydroxymethylcytosine (5hmC) in regulating transcriptomic and pathogenic mechanisms after focal ischemic injury. Methods- Young and aged male and female mice were subjected to transient middle cerebral artery occlusion, and the peri-infarct region was analyzed at various times of reperfusion. Two days before middle cerebral artery occlusion, short-interfering RNA against an isoform of the 5hmC producing enzyme TET (ten-eleven translocase) was injected intracerebrally. Ascorbate was injected intraperitoneally at 5 minutes, 30 minutes, or 2 hours of reperfusion. Motor function was tested with rotarod and beam-walk test. Results- Focal ischemia rapidly induced the activity of TET, the enzyme that catalyzes the formation of 5hmC and preferentially increased expression of the TET3 isoform in the peri-infarct region of the ischemic cortex. Levels of 5hmC were increased in a TET3-dependent manner, and inhibition of TET3 led to wide-scale reductions in the postischemic expression of neuroprotective genes involved in antioxidant defense and DNA repair. TET3 knockdown in adult male and female mice further increased brain degeneration after focal ischemia, demonstrating a role for TET3 and 5hmC in endogenous protection against stroke. Ascorbate treatment after focal ischemia enhanced TET3 activity and 5hmC enrichment in the peri-infarct region. TET3 activation by ascorbate provided robust protection against ischemic injury in young and aged mice of both sexes. Moreover, ascorbate treatment improved motor function recovery in both male and female mice. Conclusions- Collectively, these results indicate the potential of TET3 and 5hmC as novel stroke therapeutic targets. Visual Overview- An online visual overview is available for this article.

Indexed as

5-MethylcytosineAge FactorsAnimalsBrainDNADNA-Binding ProteinsEpigenesis, GeneticInfarction, Middle Cerebral ArteryMaleMiceProto-Oncogene ProteinsStroke5-hydroxymethylcytosine5-MethylcytosineDNADNA-Binding ProteinsProto-Oncogene Proteins5-hydroxymethylcytosineDNA repairfocal ischemianeuroprotectionoxidative stress

Identifiers

PMID31327315
PMCPMC6710106
OpenAlexW2964088740

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.