ArticleAmerican journal of physiology. Cell physiology2013
CORM-A1 prevents blood-brain barrier dysfunction caused by ionotropic glutamate receptor-mediated endothelial oxidative stress and apoptosis.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
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- Selective Head Cooling and NOX Inhibition Protect the Blood-Brain Barrier in Neonatal Epilepsy.Antioxidants (Basel, Switzerland) · 2025Article
- Carbon monoxide-releasing molecule-3 exerts neuroprotection effects after cardiac arrest in mice: A randomized controlled study.Resuscitation plus · 2024Article
- Kv7 channel activation reduces brain endothelial cell permeability and prevents kainic acid-induced blood-brain barrier damage.American journal of physiology. Cell physiology · 2024Article
- Physiological and Pathological Remodeling of Cerebral Microvessels.International journal of molecular sciences · 2022Review
- Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System.International journal of molecular sciences · 2022Review
- Sexually dimorphic prelimbic cortex mechanisms play a role in alcohol dependence: protection by endostatin.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?Clinical reviews in allergy & immunology · 2021Review
- Glymphatic system, AQP4, and their implications in Alzheimer's disease.Neurological research and practice · 2021Review
- Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects.Frontiers in pharmacology · 2021Article
- Acute antioxidant and cytoprotective effects of sulforaphane in brain endothelial cells and astrocytes during inflammation and excitotoxicity.Pharmacology research & perspectives · 2020Article
- Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms.Fluids and barriers of the CNS · 2020Review
- Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage.Fluids and barriers of the CNS · 2020Article
- The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review.Antioxidants (Basel, Switzerland) · 2019Review
- Potential Applications of Remote Limb Ischemic Conditioning for Chronic Cerebral Circulation Insufficiency.Frontiers in neurology · 2019Review
- The Role of NMDA Receptors in Alzheimer's Disease.Frontiers in neuroscience · 2019Review
- Astrocyte-produced carbon monoxide and the carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by prolonged neonatal asphyxia.American journal of physiology. Heart and circulatory physiology · 2018Article
- Carbon Monoxide Ameliorates 6-Hydroxydopamine-Induced Cell Death in C6 Glioma Cells.Biomolecules & therapeutics · 2018Article
- Cerebral Ischemic Postconditioning Plays a Neuroprotective Role through Regulation of Central and Peripheral Glutamate.BioMed research international · 2018Review
- Preventing harmful effects of epileptic seizures on cerebrovascular functions in newborn pigs: does sex matter?Pediatric research · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In cerebral microvascular endothelial cells (CMVEC) of newborn pigs, glutamate at excitotoxic concentrations (mM) causes apoptosis mediated by reactive oxygen species (ROS). Carbon monoxide (CO) produced by CMVEC or delivered by a CO-releasing molecule, CORM-A1, has antioxidant properties. We tested the hypothesis that CORM-A1 prevents cerebrovascular endothelial barrier dysfunction caused by glutamate excitotoxicity. First, we identified the glutamate receptors (GluRs) and enzymatic sources of ROS involved in the mechanism of endothelial apoptosis. In glutamate-exposed CMVEC, ROS formation and apoptosis were blocked by rotenone, 2-thenoyltrifluoroacetone (TTFA), and antimycin, indicating that mitochondrial complexes I, II, and III are the major sources of oxidative stress. Agonists of ionotropic GluRs (iGluRs) N-methyl-D-aspartate (NMDA), cis-ACPD, AMPA, and kainate increased ROS production and apoptosis, whereas iGluR antagonists exhibited antiapoptotic properties, suggesting that iGluRs mediate glutamate-induced endothelial apoptosis. The functional consequences of endothelial injury were tested in the model of blood-brain barrier (BBB) composed of CMVEC monolayer on semipermeable membranes. Glutamate and iGluR agonists reduced transendothelial electrical resistance and increased endothelial paracellular permeability to 3-kDa dextran. CORM-A1 exhibited potent antioxidant and antiapoptotic properties in CMVEC and completely prevented BBB dysfunction caused by glutamate and iGluR agonists. Overall, the endothelial component of the BBB is a cellular target for excitotoxic glutamate that, via a mechanism involving a iGluR-mediated activation of mitochondrial ROS production and apoptosis, leads to BBB opening that may be prevented by the antioxidant and antiapoptotic actions of CORMs. Antioxidant CORMs therapy may help preserve BBB functional integrity in neonatal cerebrovascular disease.
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