ArticleRedox biology2015
High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature.
Article in Redox biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Acute glycemic variability and short-term mortality of patients with subarachnoid hemorrhage: a meta-analysis.Frontiers in neurology · 2026Pooled it
- Deconstructing the RAGE signaling maze: the molecular key to opening a new dimension of ovarian anti-aging.Experimental & molecular medicine · 2026Review
- Upregulation of PPTC7 in brain microvascular endothelial cell aggravates diabetic cognitive dysfunction by impairing PHB2 mediated mitochondrial function.Redox biology · 2026Article
- Novel Insights into the Mechanism and Treatment of Diabetes-Related Brain Complications: Focusing on the Blood-Brain Barrier Impairment.Aging and disease · 2025Review
- Advanced Glycation End Products in Disease Development and Potential Interventions.Antioxidants (Basel, Switzerland) · 2025Review
- Increased Levels of Circulating Methylglyoxal Have No Consequence for Cerebral Microvascular Integrity and Cognitive Function in Young Healthy Mice.Molecular neurobiology · 2025Article
- Cysteinyl leukotriene receptor 1 regulates cellular glucose levels in human retinal cells.Molecular vision · 2025Article
- Observational
- Exacerbated ischemic brain damage in type 2 diabetes via methylglyoxal-mediated miR-148a-3p decline.BMC medicine · 2024Article
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Multimodal imaging of the role of hyperglycemia following experimental subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Fibroblast growth factor 21 alleviates diabetes-induced cognitive decline.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Association of Glycemic Variability With Imaging Markers of Vascular Burden, β-Amyloid, Brain Atrophy, and Cognitive Impairment.Neurology · 2024Article
- Article
- Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024Review
- Ezrin Contributes to the Damage of Airway Epithelial Barrier Related to Diabetes Mellitus.Journal of inflammation research · 2024Article
- Brain microvascular endothelial cell metabolism and its ties to barrier function.Vitamins and hormones · 2024Article
- Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity.Fluids and barriers of the CNS · 2023Review
- Plasma levels of neurology-related proteins are associated with cognitive performance in an older population with overweight/obesity and metabolic syndrome.GeroScience · 2023Article
- Near-Infrared Spectroscopy: A Free-Living Neuroscience Tool to Better Understand Diabetes and Obesity.Metabolites · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We previously demonstrated that in normal glucose (5mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG-occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG-occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes.
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What Socratic holds
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 Socratic graph.