ArticleNeurobiology of disease2017
Scavenging of highly reactive gamma-ketoaldehydes attenuates cognitive dysfunction associated with epileptogenesis.
Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- First-in-human study assessing safety, tolerability, and pharmacokinetics of 2-hydroxybenzylamine acetate, a selective dicarbonyl electrophile scavenger, in healthy volunteers.BMC pharmacology & toxicology · 2019Trial
- Novel Catalytic Antioxidant Formulation Decreases Oxidative Stress, Neuroinflammation and Cognitive Dysfunction in a Model of Nerve Agent Intoxication.The Journal of pharmacology and experimental therapeutics · 2024Article
- Cognitive comorbidities in the rat pilocarpine model of epilepsy.Frontiers in neurology · 2024Article
- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (Basel, Switzerland) · 2023Review
- Expression Pattern of ALOXE3 in Mouse Brain Suggests Its Relationship with Seizure Susceptibility.Cellular and molecular neurobiology · 2022Article
- Crosstalk between neuroinflammation and oxidative stress in epilepsy.Frontiers in cell and developmental biology · 2022Review
- Neuron-specific mitochondrial oxidative stress results in epilepsy, glucose dysregulation and a striking astrocyte response.Neurobiology of disease · 2021Article
- Isolevuglandins as mediators of disease and the development of dicarbonyl scavengers as pharmaceutical interventions.Pharmacology & therapeutics · 2020Review
- Catalpol Exerts an Anti-Epilepticus Effect, Possibly by Regulating the Nrf2-Keap1-ARE Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Pharmacological targeting of brain inflammation in epilepsy: Therapeutic perspectives from experimental and clinical studies.Epilepsia open · 2018Article
- Metabolic Dysfunction and Oxidative Stress in Epilepsy.International journal of molecular sciences · 2017Review
- Reactive Carbonyl Species Scavengers-Novel Therapeutic Approaches for Chronic Diseases.Current pharmacology reports · 2017Article
- A Metabolic Paradigm for Epilepsy.Epilepsy currentsArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cognitive dysfunction is a major comorbidity of the epilepsies; however, treatments targeting seizure-associated cognitive dysfunction, particularly deficits in learning and memory are not available. Isoketals and neuroketals, collectively known as gamma-ketoaldehydes are formed via the non-enzymatic, free radical catalyzed oxidation of arachidonic acid and docosahexaenoic acid, respectively. They are attractive candidates for oxidative protein damage and resultant cognitive dysfunction due to their formation within the plasma membrane and their high proclivity to form cytotoxic adducts on protein lysine residues. We tested the hypothesis that gamma-ketoaldehydes mechanistically contribute to seizure-associated memory impairment using a specific gamma-ketoaldehyde scavenger, salicylamine in the kainic acid and pilocarpine rat models of temporal lobe epilepsy. We show that gamma-ketoaldehydes are increased following epileptogenic injury in hippocampus and perirhinal cortex, two brain regions imperative for learning and memory. Treatment with an orally bioavailable, brain permeable scavenger, salicylamine attenuated 1) spatial memory deficits 2) reference memory deficits and 3) neuronal loss and astrogliosis in two mechanistically distinct models of epilepsy without affecting the epileptogenic injury or the development of chronic epilepsy. We have previously demonstrated that reactive oxygen species and the lipid peroxidation biomarkers, F
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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.