ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2019
Exacerbated brain edema in a rat streptozotocin model of hyperglycemic ischemic stroke: Evidence for involvement of blood-brain barrier Na-K-Cl cotransport and Na/H exchange.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- SRT1720-loaded exosome-mimetic nanovesicles promote mitophagy via SIRT1/PARKIN activation to ameliorate diabetic cerebral infarction in a preclinical rat model.International journal of pharmaceutics: X · 2026Article
- Hyperglycemia enhances brain susceptibility to lipopolysaccharide-induced neuroinflammation via astrocyte reprogramming.Journal of neuroinflammation · 2024Article
- Inhibition of HMGB1 Attenuates Spinal Cord Edema by Reducing the Expression of NaJournal of neurotrauma · 2023Article
- The stress hyperglycemia ratio is associated with the development of cerebral edema and poor functional outcome in patients with acute cerebral infarction.Frontiers in aging neuroscience · 2022Article
- Sex hormones regulate NHE1 functional expression and brain endothelial proteome to control paracellular integrity of the blood endothelial barrier.Brain research · 2021Article
- High-Fat Diet Aggravates Cerebral Infarct, Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model.International journal of molecular sciences · 2021Article
- High glucose-induced effects on NaAmerican journal of physiology. Cell physiology · 2021Article
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- Cerebral Edema Formation After Stroke: Emphasis on Blood-Brain Barrier and the Lymphatic Drainage System of the Brain.Frontiers in cellular neuroscience · 2021Review
- Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke.Pharmaceutics · 2020Review
- Functional NHE1 expression is critical to blood brain barrier integrity and sumatriptan blood to brain uptake.PloS one · 2020Article
- Endothelial Targets in Stroke: Translating Animal Models to Human.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- The interaction of zinc and the blood-brain barrier under physiological and ischemic conditions.Toxicology and applied pharmacology · 2019Review
- Neurovascular unit transport responses to ischemia and common coexisting conditions: smoking and diabetes.American journal of physiology. Cell physiology · 2019Review
- A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Review
- The peripheral immune response after stroke-A double edge sword for blood-brain barrier integrity.CNS neuroscience & therapeutics · 2018Review
- Malignant MCA Stroke: an Update on Surgical Decompression and Future Directions.Current atherosclerosis reports · 2015Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Cerebral edema is exacerbated in diabetic ischemic stroke through poorly understood mechanisms. We showed previously that blood-brain barrier (BBB) Na-K-Cl cotransport (NKCC) and Na/H exchange (NHE) are major contributors to edema formation in normoglycemic ischemic stroke. Here, we investigated whether hyperglycemia-exacerbated edema involves changes in BBB NKCC and NHE expression and/or activity and whether inhibition of NKCC or NHE effectively reduces edema and injury in a type I diabetic model of hyperglycemic stroke. Cerebral microvascular endothelial cell (CMEC) NKCC and NHE abundances and activities were determined by Western blot, radioisotopic flux and microspectrofluorometric methods. Cerebral edema and Na in rats subjected to middle cerebral artery occlusion (MCAO) were assessed by nuclear magnetic resonance methods. Hyperglycemia exposures of 1-7d significantly increased CMEC NKCC and NHE abundance and activity. Subsequent exposure to ischemic factors caused more robust increases in NKCC and NHE activities than in normoglycemic CMEC. MCAO-induced edema and brain Na uptake were greater in hyperglycemic rats. Intravenous bumetanide and HOE-642 significantly attenuated edema, brain Na uptake and ischemic injury. Our findings provide evidence that BBB NKCC and NHE contribute to increased edema in hyperglycemic stroke, suggesting that these Na transporters are promising therapeutic targets for reducing damage in diabetic stroke.
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