ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Decreased neuronal death in Na+/H+ exchanger isoform 1-null mice after in vitro and in vivo ischemia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 115 citations in OpenAlex.
- Citronellal Alleviates Cognitive Impairment by Inhibiting NHE1-Mediated Mitochondrial Damage in Vascular Dementia.Applied biochemistry and biotechnology · 2026Article
- Metformin Sensitizes PTEN-deficient Prostate Cancer to PARP Inhibitors by Rebuilding NADPInternational journal of biological sciences · 2026Article
- A dangerous liaison: Spreading depolarization and tissue acidification in cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Review
- The mitochondria as a potential therapeutic target in cerebral I/R injury.Frontiers in neuroscience · 2024Review
- The Systemic Administration of NaJournal of clinical practice and research · 2024Article
- Pharmacological Inhibition of NHE1 Protein Increases White Matter Resilience and Neurofunctional Recovery after Ischemic Stroke.International journal of molecular sciences · 2023Article
- Ischemia Reperfusion Injury Induced Blood Brain Barrier Dysfunction and the Involved Molecular Mechanism.Neurochemical research · 2023Review
- Cognitive Sequelae and Hippocampal Dysfunction in Chronic Kidney Disease following 5/6 Nephrectomy.Brain sciences · 2022Article
- Role of NaJournal of molecular medicine (Berlin, Germany) · 2022Review
- Review
- Tissue Acidosis Associated with Ischemic Stroke to Guide Neuroprotective Drug Delivery.Biology · 2020Review
- Drug development in targeting ion channels for brain edema.Acta pharmacologica Sinica · 2020Article
- Excitotoxicity: Still Hammering the Ischemic Brain in 2020.Frontiers in neuroscience · 2020Review
- Functional NHE1 expression is critical to blood brain barrier integrity and sumatriptan blood to brain uptake.PloS one · 2020Article
- HOE-642 improves the protection of hypothermia on neuronal mitochondria after cardiac arrest in rats.American journal of translational research · 2020Article
- Sodium/Hydrogen Exchanger 1 Participates in Early Brain Injury after Subarachnoid Hemorrhage bothCell transplantation · 2019Article
- Neurovascular unit transport responses to ischemia and common coexisting conditions: smoking and diabetes.American journal of physiology. Cell physiology · 2019Review
- Selective role of NaGlia · 2018Article
- Selective knockout of astrocytic NaGlia · 2018Article
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Na+/H+ exchanger isoform 1 (NHE1) is a major acid extrusion mechanism after intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to the disruption of Na+ homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Three hours of oxygen and glucose deprivation (OGD) followed by 21 h of reoxygenation (REOX) led to 68 +/- 10% cell death. Inhibition of NHE1 with the potent inhibitor cariporide (HOE 642) or genetic ablation of NHE1 reduced OGD-induced cell death by approximately 40-50% (p < 0.05). In NHE1(+/+) neurons, OGD caused a twofold increase in [Na+]i, and 60 min REOX triggered a sevenfold increase. Genetic ablation of NHE1 or HOE 642 treatment had no effects on the OGD-mediated initial Na+(i) rise but reduced the second phase of Na+(i) rise by approximately 40-50%. In addition, 60 min REOX evoked a 1.5-fold increase in [Ca2+]i in NHE1(+/+) neurons, which was abolished by inhibition of either NHE1 or reverse-mode operation of Na+/Ca2+ exchange. OGD/REOX-mediated mitochondrial Ca2+ accumulation and cytochrome c release were attenuated by inhibition of NHE1 activity. In an in vivo focal ischemic model, 2 h of left middle cerebral artery occlusion followed by 24 h of reperfusion induced 84.8 +/- 8.0 mm3 infarction in NHE1(+/+) mice. NHE1(+/+) mice treated with HOE 642 or NHE1 heterozygous mice exhibited a approximately 33% decrease in infarct size (p < 0.05). These results imply that NHE1 activity disrupts Na+ and Ca2+ homeostasis and contributes to ischemic neuronal damage.
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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 OpenQuestion graph.