ArticleMetabolic brain disease2015
Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia.
Article in Metabolic brain disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Claudin proteins and hemorrhage severity in aneurysmal subarachnoid hemorrhage: Correlation with modified Fisher score but not functional outcome.Neurosurgical review · 2025Article
- Review
- Acute severe hypoglycemia alters mouse brain microvascular proteome.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Low-Dose X-Ray Increases Paracellular Permeability of Human Renal Glomerular Endothelial Cells.Computational and mathematical methods in medicine · 2022Article
- Pericytes Suppress Brain Metastasis from Lung Cancer In Vitro.Cellular and molecular neurobiology · 2020Article
- Human ES-derived MSCs correct TNF-α-mediated alterations in a blood-brain barrier model.Fluids and barriers of the CNS · 2019Article
- Article
- Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage.International journal of molecular sciences · 2019Review
- Astrocyte-Derived Paracrine Signals: Relevance for Neurogenic Niche Regulation and Blood-Brain Barrier Integrity.Frontiers in pharmacology · 2019Review
- Aquaporin-4 deletion ameliorates hypoglycemia-induced BBB permeability by inhibiting inflammatory responses.Journal of neuroinflammation · 2018Article
- Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis.CNS neuroscience & therapeutics · 2017Article
- Simulating vasogenic brain edema using chronic VEGF infusion.Journal of neurosurgery · 2017Article
- Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery.Molecular neurobiology · 2017Review
- Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes.Metabolic brain disease · 2017Article
- Blood-brain barrier disruption and edema formation due to prolonged starvation in wild-type mice.Brain circulationArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoglycemia is a common and serious problem among patients with type 1 diabetes receiving treatment with insulin. Clinical studies have demonstrated that hypoglycemic edema is involved in the initiation of hypoglycemic brain damage. However, the mechanisms of this edema are poorly understood. Vascular endothelial growth factor (VEGF), a potent regulator of blood vessel function, has been observed an important candidate hormone induced by hypoglycemia to protect neurons by restoring plasma glucose. Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown. To investigate the effects of hypoglycemia on cerebral microvascular endothelial cells and assess the protective effect of exogenous VEGF on endothelial cells during hypoglycemia, confluent monolayers of the brain endothelial cell line bEnd.3 were treated with normal (5.5 mM glucose), hypoglycemic (0, 0.5, 1 mM glucose) medium or hypoglycemic medium in the presence of VEGF. The results clearly showed that hypoglycemia significantly downregulated the expression of claudin-5 in bEnd.3 cells, without affecting ZO-1 and occludin expression and distribution. Besides, transendothelial permeability significantly increased under hypoglycemic conditions compared to that under control conditions. Moreover, the hypoglycemic medium in presence of VEGF decreased endothelial permeability via the inhibition of claudin-5 degradation and improved hypoglycemia-induced cell toxicity. Furthermore, Glucose transporter-1 (Glut-1) and apoptosis regulator Bcl-2 expression were significantly upregulated. Taken together, hypoglycemia can significantly increase paraendocellular permeability by downregulating claudin-5 expression. We further showed that VEGF protected brain endothelial cells against hypoglycemia by enhancing glucose passage, reducing endothelial cell death, and ameliorating paraendocellular permeability.
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