ArticlePloS one2015
The Effects of Methylene Blue on Autophagy and Apoptosis in MRI-Defined Normal Tissue, Ischemic Penumbra and Ischemic Core.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Methylene blue modulates functional connectivity in the human brain.Brain imaging and behavior · 2017Trial
- Chinese prescription Kangen-karyu attenuates neuronal damage and improves cognitive function in global cerebral ischemia/reperfusion by regulating ROS-mediated MAPK activation.Frontiers in pharmacology · 2026Article
- Hepatoprotection by Methylene Blue Against Doxorubicin Toxicity Through Coordinated Modulation of Oxidative Stress, ER Stress, and Apoptotic Pathways.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Methylene Blue Mitigates Doxorubicin-Induced Cardiotoxicity via KEAP1/NRF2/GPX-4/Caspase3 Modulation.International journal of molecular sciences · 2025Article
- Effect and mechanism of Dichloroacetate in the treatment of stroke and the resolution strategy for side effect.European journal of medical research · 2025Review
- Evaluation of topical methylene blue nanoemulsion for wound healing in diabetic mice.Pharmaceutical biology · 2023Article
- Acupuncture for autophagy in animal models of middle cerebral artery occlusion: A systematic review and meta-analysis protocol.PloS one · 2023Article
- Methylene blue ameliorates brain edema in rats with experimental ischemic stroke via inhibiting aquaporin 4 expression.Acta pharmacologica Sinica · 2021Article
- Effect of Methylene Blue on White Matter Injury after Ischemic Stroke.Oxidative medicine and cellular longevity · 2021Article
- Autophagy-Associated lncRNAs: Promising Targets for Neurological Disease Diagnosis and Therapy.Neural plasticity · 2020Review
- From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue.Molecular neurobiology · 2018Review
- Methylene Blue Exerts Anticonvulsant and Neuroprotective Effects on Self-Sustaining Status Epilepticus (SSSE) Induced by Prolonged Basolateral Amygdala Stimulation in Wistar Rats.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Chronic oral methylene blue treatment in a rat model of focal cerebral ischemia/reperfusion.Brain research · 2018Article
- Oral administration of ampelopsin protects against acute brain injury in rats following focal cerebral ischemia.Experimental and therapeutic medicine · 2017Article
- MEF2D Mediates the Neuroprotective Effect of Methylene Blue Against Glutamate-Induced Oxidative Damage in HT22 Hippocampal Cells.Molecular neurobiology · 2017Article
- Neuroprotective and Functional Improvement Effects of Methylene Blue in Global Cerebral Ischemia.Molecular neurobiology · 2016Article
- Autophagy in acute brain injury.Nature reviews. Neuroscience · 2016Review
- Methylene blue and normobaric hyperoxia combination therapy in experimental ischemic stroke.Brain and behavior · 2016Article
- Targeting oxidative stress for the treatment of ischemic stroke: Upstream and downstream therapeutic strategies.Brain circulationReview
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Methylene blue (MB) USP, which has energy-enhancing and antioxidant properties, is currently used to treat methemoglobinemia and cyanide poisoning in humans. We recently showed that MB administration reduces infarct volume and behavioral deficits in rat models of ischemic stroke and traumatic brain injury. This study reports the underlying molecular mechanisms of MB neuroprotection following transient ischemic stroke in rats. Rats were subjected to transient (60-mins) ischemic stroke. Multimodal MRI during the acute phase and at 24 hrs were used to define three regions of interest (ROIs): i) the perfusion-diffusion mismatch salvaged by reperfusion, ii) the perfusion-diffusion mismatch not salvaged by reperfusion, and iii) the ischemic core. The tissues from these ROIs were extracted for western blot analyses of autophagic and apoptotic markers. The major findings were: 1) MB treatment reduced infarct volume and behavioral deficits, 2) MB improved cerebral blood flow to the perfusion-diffusion mismatch tissue after reperfusion and minimized harmful hyperperfusion 24 hrs after stroke, 3) MB inhibited apoptosis and enhanced autophagy in the perfusion-diffusion mismatch, 4) MB inhibited apoptotic signaling cascades (p53-Bax-Bcl2-Caspase3), and 5) MB enhanced autophagic signaling cascades (p53-AMPK-TSC2-mTOR). MB induced neuroprotection, at least in part, by enhancing autophagy and reducing apoptosis in the perfusion-diffusion mismatch tissue following ischemic stroke.
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Registered trials
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.