ArticleNeurocritical care2014
pH-sensitive NMDA inhibitors improve outcome in a murine model of SAH.
Article in Neurocritical care, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Experimental-Clinical Disconnect and the Unmet Need.Neurocritical care · 2020Pooled it
- A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.Translational stroke research · 2017Pooled it
- A Novel Anti-Inflammatory Small Molecule MW189 Reduces Microglial Activation and Improves Functional Outcomes in a Murine Model of Subarachnoid Hemorrhage.Neurocritical care · 2026Article
- Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage.Free radical biology & medicine · 2024Article
- Incidence and Factors in Delayed Neurological Deficits after Subarachnoid Hemorrhage in Mice.Brain hemorrhages · 2024Article
- Phase 1 Clinical Results for NP10679, a pH-sensitive GluN2B-selective N-methyl-d-aspartate Receptor Inhibitor.Clinical pharmacology in drug development · 2023Article
- Novel GluN2B-Selective NMDA Receptor Negative Allosteric Modulator Possesses Intrinsic Analgesic Properties and Enhances Analgesia of Morphine in a Rodent Tail Flick Pain Model.ACS chemical neuroscience · 2023Article
- Ifenprodil Improves Long-Term Neurologic Deficits Through Antagonizing Glutamate-Induced Excitotoxicity After Experimental Subarachnoid Hemorrhage.Translational stroke research · 2021Article
- A GlutamateThe Journal of pharmacology and experimental therapeutics · 2021Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score.Journal of the American Heart Association · 2019Article
- Structural elements of a pH-sensitive inhibitor binding site in NMDA receptors.Nature communications · 2019Article
- Apolipoprotein E mimetic peptide CN-105 improves outcome in a murine model of SAH.Stroke and vascular neurology · 2018Article
- Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Review
- Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Transient receptor potential channel 1/4 reduces subarachnoid hemorrhage-induced early brain injury in rats via calcineurin-mediated NMDAR and NFAT dephosphorylation.Scientific reports · 2016Article
- Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors.Brain, behavior, and immunity · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDespite intensive research, neurological morbidity from delayed cerebral ischemia remains common after aneurysmal subarachnoid hemorrhage (SAH). In the current study, we evaluate the neuroprotective effects of a pH-dependent GluN2B subunit-selective NMDA receptor antagonist in a murine model of SAH.
methodsFollowing induction of SAH, 12 ± 2 week old male C57-BL/6 mice received NP10075, a pH-dependent NMDA receptor antagonist, or vehicle. In a separate series of experiments, NP10075 and the non-pH sensitive NMDA antagonist, NP10191, were administered to normoglycemic and hyperglycemic mice. Both histological (right middle cerebral artery diameter, NeuN, and Fluoro-Jade B staining) and functional endpoints (rotarod latency and neuroseverity score) were evaluated to assess the therapeutic benefit of NP10075.
resultsAdministration of NP10075 was well tolerated and had minimal hemodynamic effects following SAH. Administration of the pH-sensitive NMDA antagonist NP10075, but not NP10191, was associated with a durable improvement in the functional performance of both normoglycemic and hyperglycemic animals. NP10075 was also associated with a reduction in vasospasm in the middle cerebral artery associated with hemorrhage. There was no significant difference between treatment with nimodipine + NP10075, as compared to NP10075 alone.
conclusionsThese data demonstrate that use of a pH-dependent NMDA antagonist has the potential to work selectively in areas of ischemia known to undergo acidic pH shifts, and thus may be associated with selective regional efficacy and fewer behavioral side effects than non-selective NMDA antagonists.
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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.