ArticleAmerican journal of physiology. Cell physiology2009
Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressin.
Article in American journal of physiology. Cell physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
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- Tjap1/Pilt Is a cis-Golgi-Associated Protein Required for Golgi Integrity and Normal Drug Transporter Expression in Brain Microvascular Endothelial Cells In Vitro.Pharmaceutics · 2026Article
- Mapping the transcriptional and epigenetic landscape of organotypic endothelial diversity in the developing and adult mouse.Nature cardiovascular research · 2025Article
- The role of oxidative stress in blood-brain barrier disruption during ischemic stroke: Antioxidants in clinical trials.Biochemical pharmacology · 2024Review
- Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.Aging and disease · 2024Review
- Alterations in brain fluid physiology during the early stages of development of ischaemic oedema.Fluids and barriers of the CNS · 2024Review
- Inhibition of HMGB1 Attenuates Spinal Cord Edema by Reducing the Expression of NaJournal of neurotrauma · 2023Article
- Inhibition of intracellular proton-sensitive CaActa pharmaceutica Sinica. B · 2022Article
- A new perspective on cerebrospinal fluid dynamics after subarachnoid hemorrhage: From normal physiology to pathophysiological changes.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.International journal of molecular sciences · 2022Review
- Lack of NHE6 and Inhibition of NKCC1 Associated With Increased Permeability in Blood Labyrinth Barrier-Derived Endothelial Cell Layer.Frontiers in cellular 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 glucose-induced effects on NaAmerican journal of physiology. Cell physiology · 2021Article
- Cerebral Edema Formation After Stroke: Emphasis on Blood-Brain Barrier and the Lymphatic Drainage System of the Brain.Frontiers in cellular neuroscience · 2021Review
- Functional NHE1 expression is critical to blood brain barrier integrity and sumatriptan blood to brain uptake.PloS one · 2020Article
- Potential Therapies for Cerebral Edema After Ischemic Stroke: A Mini Review.Frontiers in aging neuroscience · 2020Review
- 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.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection.American journal of physiology. Cell physiology · 2018Review
- Fluid and ion transfer across the blood-brain and blood-cerebrospinal fluid barriers; a comparative account of mechanisms and roles.Fluids and barriers of the CNS · 2016Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Blood-brain barrier (BBB) Na transporters are essential for brain water and electrolyte homeostasis. However, they also contribute to edema formation during the early hours of ischemic stroke by increased transport of Na from blood into brain across an intact BBB. We previously showed that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia, aglycemia, and AVP and that inhibition of the cotransporter by intravenous bumetanide significantly reduces edema and infarct in the rat middle cerebral artery occlusion (MCAO) model of stroke. More recently, we found evidence that intravenous cariporide (HOE-642), a highly potent Na/H exchange inhibitor, also reduces brain edema after MCAO. The present study was conducted to investigate which Na/H exchange protein isoforms are present in BBB endothelial cells and to evaluate the effects of ischemic factors on BBB Na/H exchange activity. Western blot analysis of bovine cerebral microvascular endothelial cells (CMEC) and immunoelectron microscopy of perfusion-fixed rat brain revealed that Na/H exchanger isoforms 1 and 2 (NHE1 and NHE2) are present in BBB endothelial cells. Using microspectrofluorometry and the pH-sensitive dye BCECF, we found that hypoxia (2% O(2), 30 min), aglycemia (30 min), and AVP (1-200 nM, 5 min) significantly increased CMEC Na/H exchange activity, assessed as Na-dependent, HOE-642-sensitive H(+) flux. We found that AVP stimulation of CMEC Na/H exchange activity is dependent on intracellular Ca concentration and is blocked by V(1), but not V(2), vasopressin receptor antagonists. Our findings support the hypothesis that a BBB Na/H exchanger, possibly NHE1 and/or NHE2, is stimulated during ischemia to participate in cerebral edema formation.
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