ArticleStroke2018
Critical Role of Flavin and Glutathione in Complex I-Mediated Bioenergetic Failure in Brain Ischemia/Reperfusion Injury.
Article in Stroke, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Glutathione in Skin Aging and Tissue Regeneration: A Systematic Review of Molecular Mechanisms, Redox Modulation, and Biomedical Implications.Molecules (Basel, Switzerland) · 2026Pooled it
- Efficacy of Tiaoqiheying decoction in the treatment of spasmodic pain and lipid metabolism after acute ischemic stroke.The Journal of international medical research · 2020Trial
- Suitability of a Fluorescence Method for Flavin Mononucleotide Determination in Modified HTK-Based Perfusion Solutions During Hypothermic Oxygenated Perfusion of Liver Grafts.Methods and protocols · 2026Article
- Neuroprotective potential ofVeterinary world · 2026Review
- Graft quality assessment during machine perfusion in liver transplantation: a review of current evidence and emerging strategies.Frontiers in transplantation · 2026Review
- Edaravone: Advances on cytoprotective effects, pharmacological properties, and mechanisms of action.Pharmacological reviews · 2026Review
- Microvascular dysfunction and aberrant network activity drive reduced brain oxygenation in a mouse tauopathy model.Research square · 2025Article
- Plasma Cystine as a Marker of Acute Stroke Severity.Diagnostics (Basel, Switzerland) · 2025Article
- Rescuing Ischemic Brain Injury by Rewiring Mitochondrial Electron Flow.bioRxiv : the preprint server for biology · 2025Article
- Role of mitochondrial metabolism in ischemic stroke and natural products intervention.Molecular biology reports · 2025Review
- The Influence of Oxidative Stress Markers in Patients with Ischemic Stroke.Biomolecules · 2024Review
- Review
- Specific NOX4 Inhibition Preserves Mitochondrial Function and Dampens Kidney Dysfunction Following Ischemia-Reperfusion-Induced Kidney Injury.Antioxidants (Basel, Switzerland) · 2024Article
- The mitochondria as a potential therapeutic target in cerebral I/R injury.Frontiers in neuroscience · 2024Review
- NADJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Real-time assessment of kidney allografts during HOPE using flavin mononucleotide (FMN) - a preclinical study.Frontiers in transplantation · 2023Article
- Article
- Viability Criteria during Liver Ex-Situ Normothermic and Hypothermic Perfusion.Medicina (Kaunas, Lithuania) · 2022Review
- ND3 Cys39 in complex I is exposed during mitochondrial respiration.Cell chemical biology · 2022Article
- The Impact of Genetic Polymorphisms in Glutamate-Cysteine Ligase, a Key Enzyme of Glutathione Biosynthesis, on Ischemic Stroke Risk and Brain Infarct Size.Life (Basel, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeIschemic brain injury is characterized by 2 temporally distinct but interrelated phases: ischemia (primary energy failure) and reperfusion (secondary energy failure). Loss of cerebral blood flow leads to decreased oxygen levels and energy crisis in the ischemic area, initiating a sequence of pathophysiological events that after reoxygenation lead to ischemia/reperfusion (I/R) brain damage. Mitochondrial impairment and oxidative stress are known to be early events in I/R injury. However, the biochemical mechanisms of mitochondria damage in I/R are not completely understood.
methodsWe used a mouse model of transient focal cerebral ischemia to investigate acute I/R-induced changes of mitochondrial function, focusing on mechanisms of primary and secondary energy failure.
resultsIschemia induced a reversible loss of flavin mononucleotide from mitochondrial complex I leading to a transient decrease in its enzymatic activity, which is rapidly reversed on reoxygenation. Reestablishing blood flow led to a reversible oxidative modification of mitochondrial complex I thiol residues and inhibition of the enzyme. Administration of glutathione-ethyl ester at the onset of reperfusion prevented the decline of complex I activity and was associated with smaller infarct size and improved neurological outcome, suggesting that decreased oxidation of complex I thiols during I/R-induced oxidative stress may contribute to the neuroprotective effect of glutathione ester.
conclusionsOur results unveil a key role of mitochondrial complex I in the development of I/R brain injury and provide the mechanistic basis for the well-established mitochondrial dysfunction caused by I/R. Targeting the functional integrity of complex I in the early phase of reperfusion may provide a novel therapeutic strategy to prevent tissue injury after 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.