ArticleFree radical biology & medicine2018
Development of a reactive oxygen species-sensitive nitric oxide synthase inhibitor for the treatment of ischemic stroke.
Article in Free radical biology & medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors-A review.Food science & nutrition · 2024Review
- Elevated Calcium after Acute Ischemic Stroke Predicts Severity and Prognosis.Molecular neurobiology · 2024Article
- NLRP3 inflammasome activation increases brain oxidative stress after transient global cerebral ischemia in rats.The International journal of neuroscience · 2023Article
- Neuroprotection of NADFrontiers in pharmacology · 2023Article
- Synthesis and Pharmacological Evaluation of Novel Triazole-Pyrimidine Hybrids as Potential Neuroprotective and Anti-neuroinflammatory Agents.Pharmaceutical research · 2023Article
- Therapeutic potential of nitric oxide synthase inhibitor from natural sources for the treatment of ischemic stroke.Saudi journal of biological sciences · 2022Article
- Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP).Experimental neurobiology · 2021Article
- Anti-Inflammatory Effects of a Polyphenol, Catechin-7,4'-Pharmaceutics · 2021Article
- Small molecules targeting cyclooxygenase/prostanoid cascade in experimental brain ischemia: Do they translate?Medicinal research reviews · 2021Review
- Repetitive Transcranial Magnetic Stimulation Improves Neuropathy and Oxidative Stress Levels in Rats with Experimental Cerebral Infarction through the Nrf2 Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Cerebral Ischemia-Reperfusion Is Associated With Upregulation of Cofilin-1 in the Motor Cortex.Frontiers in cell and developmental biology · 2021Article
- Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2020Article
- CKLF1 Aggravates Focal Cerebral Ischemia Injury at Early Stage Partly by Modulating Microglia/Macrophage Toward M1 Polarization Through CCR4.Cellular and molecular neurobiology · 2019Article
- Anti-inflammatory Effects of Traditional Chinese Medicines on PreclinicalFrontiers in pharmacology · 2019Review
- Prognostic Value of Oxidative Stress Markers in Patients with Pulmonary Arterial or Chronic Thromboembolic Pulmonary Hypertension.Oxidative medicine and cellular longevity · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Ischemic stroke is caused by a blockage of cerebral blood flow resulting in neuronal and glial hypoxia leading to inflammatory and reactive oxygen species (ROS)-mediated cell death. Nitric oxide (NO) formed by NO synthase (NOS) is known to be protective in ischemic stroke, however NOS has been shown to 'uncouple' under oxidative conditions to instead produce ROS. Nitrones are antioxidant molecules that are shown to trap ROS to then decompose and release NO. In this study, the nitrone 5 was designed such that its decomposition product is a NOS inhibitor, 6, effectively leading to NOS inhibition specifically at the site of ROS production. The ability of 5 to spin-trap radicals and decompose to 6 was observed using EPR and LC-MS/MS. The pro-drug concept was tested in vitro by measuring cell viability and 6 formation in SH-SY5Y cells subjected to oxygen glucose deprivation (OGD). 5 was found to be more efficacious and more potent than PBN, and was able to increase phospho-Akt while reducing nitrotyrosine and cleaved caspase-3 levels. 6 treatment, but not 5, was found to decrease NO production in LPS-stimulated microglia. Doppler flowmetry on anesthetized mice showed increased cerebral blood flow upon intravenous administration of 1mg/kg of 5, but a return to baseline upon administration of 10mg/kg, likely due to its dual nature of antioxidant/NO-donor and NOS-inhibition. Mice treated with 5 after permanent ischemia exhibited a >30% reduction in infarct volume, and higher formation of 6 in ischemic tissue resulting in region specific effects limited to the infarct area.
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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.