Evidence map›Paper›PMID 26047733›Full record

ArticleNeuroscience2015

Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress.

M-G Ryou, G R Choudhury, W Li, A Winters, F Yuan, R Liu, S-H Yang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

35 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
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  8. HIF‑1α in cerebral ischemia (Review).Molecular medicine reports · 2022
    Review
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  20. Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
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

7 authors at 3 institutions in 2 countries.

M-G RyouDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA; Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address: myoung-gwi.ryou@unthsc.edu.
G R ChoudhuryDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
W LiDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
A WintersDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
F YuanDepartment of Neurosurgery, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
R LiuDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
S-H YangDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA; Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Neurosurgery, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: shaohua.yang@unthsc.edu.
University of North Texas Health Science Center · USBeijing Institute of Neurosurgery · CNUniversity of North Texas · US

Funding

Neuroglobin: cell metabolism and neuroprotectionR01NS088596 · NINDS · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI YANG, SHAOHUA · 2014 to 2018
$1.6M
Vascular Cognitive Impairment Induced by Ischemic Stroke: mechanism and therapyR01NS054651 · NINDS · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI YANG, SHAOHUA · 2008 to 2012
$1.6M
NINDS NIH HHS R01 NS054651NINDS NIH HHS R01NS054651NINDS NIH HHS R01 NS088596NINDS NIH HHS R01NS088596
6 · The paper itself

Abstract

unlabelledBrain ischemia and reperfusion (I/R) injury occurs in various pathological conditions, but there is no effective treatment currently available in clinical practice. Methylene blue (MB) is a century-old drug with a newly discovered protective function in the ischemic stroke model. In the current investigation we studied the MB-induced neuroprotective mechanism focusing on stabilization and activation of hypoxia-inducible factor-1α (HIF-1α) in an in vitro oxygen and glucose deprivation (OGD)-reoxygenation model.

methodsHT22 cells were exposed to OGD (0.1% O2, 6h) and reoxygenation (21% O2, 24h). Cell viability was determined with the calcein AM assay. The dynamic change of intracellular O2 concentration was monitored by fluorescence lifetime imaging microscopy (FLTIM). Glucose uptake was quantified using the 2-[N-(7-Nitrobenz-2-Oxa-1,3-Diazol-4-yl)Amino]-2-Deoxy-d-Glucose (2-NBDG) assay. ATP concentration and glycolytic enzyme activity were examined by spectrophotometry. Protein content changes were measured by immunoblot: HIF-1α, prolyl hydroxylase 2 (PHD2), erythropoietin (EPO), Akt, mTOR, and PIP5K. The contribution of HIF-1α activation in the MB-induced neuroprotective mechanism was confirmed by blocking HIF-1α activation with 2-methoxyestradiol-2 (2-MeOE2) and by transiently transfecting constitutively active HIF-1α.

resultsMB increases cell viability by about 50% vs. OGD control. Compared to the corresponding control, MB increases intracellular O2 concentration and glucose uptake as well as the activities of hexokinase and G-6-PDH, and ATP concentration. MB activates the EPO signaling pathway with a corresponding increase in HIF-1α. Phosphorylation of Akt was significantly increased with MB treatment followed by activation of the mTOR pathway. Importantly, we observed, MB increased nuclear translocation of HIF-1α vs. control (about three folds), which was shown by a ratio of nuclear:cytoplasmic HIF-1α protein content.

conclusionWe conclude that MB protects the hippocampus-derived neuronal cells against OGD-reoxygenation injury by enhancing energy metabolism and increasing HIF-1α protein content accompanied by an activation of the EPO signaling pathway.

Indexed as

Adenosine TriphosphateAnimalsCell HypoxiaCell LineGlucoseHippocampusHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Ischemia, BrainMethylene BlueMice, Inbred C57BLNeuroprotective AgentsOxygenReperfusion InjuryStress, PhysiologicalAdenosine TriphosphateGlucoseHypoxia-Inducible Factor 1, alpha SubunitMethylene BlueNeuroprotective AgentsOxygenhypoxia-inducible factorischemia and reperfusion injurymethylene blueneuroprotectionoxygen and glucose deprivation

Identifiers

PMID26047733
PMCPMC4504792
OpenAlexW567021032

What OpenQuestion holds

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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.