ArticleFree radical biology & medicine2014
The neuroprotective properties of the superoxide dismutase mimetic tempol correlate with its ability to reduce pathological glutamate release in a rodent model of stroke.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Superoxide Dismutase Administration: A Review of Proposed Human Uses.Molecules (Basel, Switzerland) · 2021Pooled it
- Modulation of mitochondrial dysfunction: Mechanisms and strategies for the use of natural products to treat stroke.Neural regeneration research · 2026Article
- TEMPOL Enhances Polyethylene Glycol Axon Fusion Following Sciatic Nerve Transection in Adult Rats.ACS chemical neuroscience · 2026Article
- Therapeutic Approaches for Toxic Optic Neuropathies: Insights from Methanol-Induced Optic Neuropathy and NAION Treatments.Diagnostics (Basel, Switzerland) · 2025Review
- Non-Electrophilic Activation of NRF2 in Neurological Disorders: Therapeutic Promise of Non-Pharmacological Strategies.Antioxidants (Basel, Switzerland) · 2025Review
- Reactive Astrocytes Release GDNF to Promote Brain Recovery and Neuronal Survival Following Ischemic Stroke.Neurochemical research · 2025Article
- The role of oxidative stress in blood-brain barrier disruption during ischemic stroke: Antioxidants in clinical trials.Biochemical pharmacology · 2024Review
- Neuroprotective and immunomodulatory effects of superoxide dismutase on SH-SY5Y neuroblastoma cells and RAW264.7 macrophages.PloS one · 2024Article
- SIRT1-regulated ROS generation activates NMDAR2B phosphorylation to promote central sensitization and allodynia in a male chronic migraine rat model.Frontiers in molecular neuroscience · 2024Article
- Influence of DNP Polarizing Agents on Biochemical Processes: TEMPOL in Transient Ischemic Stroke.ACS chemical neuroscience · 2023Article
- Tempol and silymarin rescue from zinc-induced degeneration of dopaminergic neurons through modulation of oxidative stress and inflammation.Molecular and cellular biochemistry · 2023Article
- Conditional deletion of LRRC8A in the brain reduces stroke damage independently of swelling-activated glutamate release.iScience · 2023Article
- Probiotic as a Potential Gut Microbiome Modifier for Stroke Treatment: A Systematic Scoping Review of In Vitro and In Vivo Studies.Nutrients · 2022Article
- SOCE-mediated NFAT1-NOX2-NLRP1 inflammasome involves in lipopolysaccharide-induced neuronal damage and Aβ generation.Molecular neurobiology · 2022Article
- Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders.Cells · 2022Review
- Unifying mechanism behind the onset of acquired epilepsy.Trends in pharmacological sciences · 2022Review
- Low Serum Superoxide Dismutase Is Associated With a High Risk of Cognitive Impairment After Mild Acute Ischemic Stroke.Frontiers in aging neuroscience · 2022Article
- Late adolescence mortality in mice with brain-specific deletion of the volume-regulated anion channel subunit LRRC8A.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Aβ initiates brain hypometabolism, network dysfunction and behavioral abnormalities via NOX2-induced oxidative stress in mice.Communications biology · 2021Article
- Edaravone at high concentrations attenuates cognitive dysfunctions induced by abdominal surgery under general anesthesia in aged mice.Metabolic brain disease · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The contribution of oxidative stress to ischemic brain damage is well established. Nevertheless, for unknown reasons, several clinically tested antioxidant therapies have failed to show benefits in human stroke. Based on our previous in vitro work, we hypothesized that the neuroprotective potency of antioxidants is related to their ability to limit the release of the excitotoxic amino acids glutamate and aspartate. We explored the effects of two antioxidants, tempol and edaravone, on amino acid release in the brain cortex, in a rat model of transient occlusion of the middle cerebral artery (MCAo). Amino acid levels were quantified using a microdialysis approach, with the probe positioned in the ischemic penumbra as verified by a laser Doppler technique. Two-hour MCAo triggered a dramatic increase in the levels of glutamate, aspartate, taurine, and alanine. Microdialysate delivery of 10mM tempol reduced the amino acid release by 60-80%, whereas matching levels of edaravone had no effect. In line with these data, an intracerebroventricular injection of tempol but not edaravone (500 nmol each, 15 min before MCAo) reduced infarction volumes by ~50% and improved neurobehavioral outcomes. In vitro assays showed that tempol was superior at removing superoxide anion, whereas edaravone was more potent at scavenging hydrogen peroxide, hydroxyl radical, and peroxynitrite. Overall, our data suggest that the neuroprotective properties of tempol are probably related to its ability to reduce tissue levels of the superoxide anion and pathological glutamate release and, in such a way, limit progression of brain infarction within ischemic penumbra. These new findings may be instrumental in developing new antioxidant therapies for treatment of stroke.
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Registered trials
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