Evidence map›Paper›PMID 25013017›Full record

ArticleStroke2014

Mammalian target of rapamycin cell signaling pathway contributes to the protective effects of ischemic postconditioning against stroke.

Rong Xie, Peng Wang, Michelle Cheng, Robert Sapolsky, Xunming Ji, Heng Zhao

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

Article in Stroke, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 45 citations in OpenAlex.

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  7. Neuroprotective effect of ischemic postconditioning against hyperperfusion and its mechanisms of neuroprotection.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2024
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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.

Rong XieFrom the Departments of Neurosurgery (R.X., P.W., M.C., R.S., H.Z.) and Biological Sciences (M.C., R.S.), and Stanford Stroke Center (H.Z.), Stanford University, CA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (R.X.); and Department of Neurosurgery, Xuanwu Hospital, Capital Medical School, Beijing, China (P.W., X.J.).
Peng WangFrom the Departments of Neurosurgery (R.X., P.W., M.C., R.S., H.Z.) and Biological Sciences (M.C., R.S.), and Stanford Stroke Center (H.Z.), Stanford University, CA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (R.X.); and Department of Neurosurgery, Xuanwu Hospital, Capital Medical School, Beijing, China (P.W., X.J.).
Michelle ChengFrom the Departments of Neurosurgery (R.X., P.W., M.C., R.S., H.Z.) and Biological Sciences (M.C., R.S.), and Stanford Stroke Center (H.Z.), Stanford University, CA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (R.X.); and Department of Neurosurgery, Xuanwu Hospital, Capital Medical School, Beijing, China (P.W., X.J.).
Robert SapolskyFrom the Departments of Neurosurgery (R.X., P.W., M.C., R.S., H.Z.) and Biological Sciences (M.C., R.S.), and Stanford Stroke Center (H.Z.), Stanford University, CA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (R.X.); and Department of Neurosurgery, Xuanwu Hospital, Capital Medical School, Beijing, China (P.W., X.J.).
Xunming JiFrom the Departments of Neurosurgery (R.X., P.W., M.C., R.S., H.Z.) and Biological Sciences (M.C., R.S.), and Stanford Stroke Center (H.Z.), Stanford University, CA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (R.X.); and Department of Neurosurgery, Xuanwu Hospital, Capital Medical School, Beijing, China (P.W., X.J.). hzhao@stanford.edu jixm70@hotmail.com.
Heng ZhaoFrom the Departments of Neurosurgery (R.X., P.W., M.C., R.S., H.Z.) and Biological Sciences (M.C., R.S.), and Stanford Stroke Center (H.Z.), Stanford University, CA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (R.X.); and Department of Neurosurgery, Xuanwu Hospital, Capital Medical School, Beijing, China (P.W., X.J.). hzhao@stanford.edu jixm70@hotmail.com.
Huashan Hospital · CNFudan University · CN

Funding

Protective mechanisms of ischemic postconditioningR01NS064136 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2010 to 2020
$3.1M
NINDS NIH HHS 1R01NS064136-01NINDS NIH HHS R01 NS064136
6 · The paper itself

Abstract

background and purposeWhether the mammalian target of rapamycin (mTOR) pathway is protective against brain injury from stroke or is detrimental is controversial, and whether it is involved in the protective effects of ischemic postconditioning (IPC) against stroke is unreported. Our study focuses on the protective role of mTOR against neuronal injury after stroke with and without IPC.

methodsWe used both an in vitro oxygen-glucose deprivation model with a mixed neuronal culture and hypoxic postconditioning, as well as an in vivo stroke model with IPC. Rapamycin, a specific pharmacological inhibitor of mTOR, and mTOR short hairpin RNA lentiviral vectors were used to inhibit mTOR activity. A lentiviral vector expressing S6K1, a downstream molecule of mTOR, was used to confirm the protective effects of mTOR. Infarct sizes were measured and protein levels were examined by Western blot.

resultsWe report that stroke resulted in reduced levels of phosphorylated proteins in the mTOR pathway, including S6K1, S6, and 4EBP1, and that IPC increased these proteins. mTOR inhibition, both by the mTOR inhibitor rapamycin and by mTOR short hairpin RNA, worsened ischemic outcomes in vitro and in vivo and abolished the protective effects of hypoxic postconditioning and IPC on neuronal death in vitro and brain injury size in vivo. Overexpression of S6K1 mediated by lentiviral vectors significantly attenuated brain infarction.

conclusionsmTOR plays a crucial protective role in brain damage after stroke and contributes to the protective effects of IPC.

Indexed as

Signal TransductionAnimalsBlood GlucoseBrainCell SurvivalGlucoseHypoxiaIschemic PostconditioningLentivirusNeuronsOxygenPhosphorylationRatsRibosomal Protein S6 KinasesRNASirolimusBlood GlucoseGlucosemTOR protein, ratOxygenRibosomal Protein S6 KinasesRNARps6kb1 protein, ratSirolimusTOR Serine-Threonine Kinasesischemic postconditioningstroke

Identifiers

PMID25013017
PMCPMC4146669
OpenAlexW2012886371

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.