ArticleStroke2011
Carbon monoxide-activated Nrf2 pathway leads to protection against permanent focal cerebral ischemia.
Article in Stroke, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 2 of them syntheses 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
114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Pooled it
- Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis.Scientific reports · 2016Pooled it
- Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer's and Parkinson's diseases.Redox report : communications in free radical research · 2026Review
- Bilirubin and the Yellow Players in Ferroptosis: A Delicate Balance in Human Health and Disease, with a Focus on the Liver, Cardiovascular System, and Brain.Biomolecules · 2026Review
- Neuroprotection with Hemoglobin-based Oxygen Carriers in Ischemic Stroke: A Narrative Review of Preclinical Studies.JMA journal · 2026Review
- Exercise and smoking: health rivals revealing shared protective mechanisms in Parkinson's?NPJ Parkinson's disease · 2026Review
- Gas entrapping materials for damage control.Advanced drug delivery reviews · 2026Review
- Carbon Monoxide Therapy: Evidence and Prospects for Preventing and Treating Retinal Diseases.Biomolecules · 2026Review
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- The role of gasotransmitters in Parkinson's disease: Interplay of nitric oxide, carbon monoxide, and hydrogen sulfide.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide.Medicinal research reviews · 2025Review
- Opinion: exploring alternative pathways to neuroprotection-nicotine and carbon monoxide as antioxidative factors in neurodegeneration and delirium.Frontiers in neurology · 2025Article
- Air pollution and adult hospital admissions for ischemic stroke: a time-series analysis in Inner Mongolia, China.Environmental health and preventive medicine · 2025Observational
- Significance of nicotine and nicotinic acetylcholine receptors in Parkinson's disease.Frontiers in aging neuroscience · 2025Review
- Metal-Free CO Prodrugs Activated by Molecular Oxygen Protect against Doxorubicin-Induced Cardiomyopathy in Mice.Journal of medicinal chemistry · 2024Article
- The Protective Role of Transcript-Induced in Spermiogenesis 40 in Cerebral Ischemia-Reperfusion Injury.Neurochemical research · 2024Article
- Neuroprotection of low dose carbon monoxide in Parkinson's disease models commensurate with the reduced risk of Parkinson's among smokers.NPJ Parkinson's disease · 2024Article
- Interaction between ambient CO and temperature or relative humidity on the risk of stroke hospitalization.Scientific reports · 2024Article
- Recent advances in the application of gasotransmitters in spinal cord injury.Journal of nanobiotechnology · 2024Review
- Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.Journal of the American Heart Association · 2024Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeCarbon monoxide (CO) is a gaseous second messenger produced when heme oxygenase enzymes catabolize heme. We have demonstrated that CO can be therapeutic in ischemia-reperfusion brain injury; however, it is unclear whether CO can also offer protection in permanent ischemic stroke or what mechanism(s) underlies the effect. Heme oxygenase-1 neuroprotection was shown to be regulated by Nrf2; therefore, we investigated whether CO might partially exert neuroprotection by modulating the Nrf2 pathway.
methodsTo evaluate the potential protective effects of CO, we exposed male wild-type and Nrf2-knockout mice to 250 ppm CO or control air for 18 hours immediately after permanent middle cerebral artery occlusion. Infarct volume and neurologic deficits were assessed on day 7. Molecular mechanisms of Nrf2 pathway activation by CO were also investigated.
resultsMice exposed to CO after permanent ischemia had 29.6±12.6% less brain damage than did controls at 7 days, although amelioration in neurologic deficits did not reach significance. Additionally, 18-hour CO treatment led to Nrf2 dissociation from Keap1, nuclear translocation, increased binding activity of Nrf2 to heme oxygenase-1 antioxidant response elements, and elevated heme oxygenase-1 expression 6 to 48 hours after CO exposure. The CO neuroprotection was completely abolished in Nrf2-knockout mice.
conclusionsLow-concentration CO represent a neuroprotective agent for combination treatment of ischemic stroke, and its beneficial effect would be at least partially mediated by activation of the Nrf2 pathway.
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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.