Original Research
Exp. Biol. Med.
Sec. Pharmacology and Toxicology
Volume 250 - 2025 | doi: 10.3389/ebm.2025.10598
This article is part of the Issue2024 International Conference on Neuroprotective Agents Conference ProceedingsView all 12 articles
Cystamine reduces neurodegeneration and epileptogenesis following soman-induced status epilepticus in rats
Abiel K Biney
Caroline R Schultz
Michael F Stone
Donna A NguyenAnnie WangMarcio De Araujo Furtado
Lucille Lumley*- US Army Medical Research Institute of Chemical Defense, Aberdeen, Maryland, United States
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Background: Acute exposure to a seizure-inducing dose of an organophosphorus nerve agent inhibits acetylcholinesterase, leading to pharmacoresistance if benzodiazepine treatment is delayed.Following soman-induced status epilepticus (SE) in rats, prolonged seizure is associated with severe and widespread neurodegeneration. We evaluated the aminothiol cystamine, the oxidized form of cysteamine, for neuroprotective potential against soman-induced SE and associated neurodegeneration. Cystamine has a myriad of effects including antioxidant properties, neuroprotective effects, and immunomodulation, among others, which is of interest in evaluating neuroprotective efficacy against cholinergic-induced neurodegeneration. Methods: Adult male rats implanted with telemetry transmitters for continuous EEG recording were exposed to soman and treated with the muscarinic antagonist atropine sulfate and the oxime asoxime dimethanesulfonate 1 min after exposure to increase survival and with midazolam 30 min after seizure onset. Cystamine (10 or 50 mg/kg) or vehicle was administered 30 min after seizure onset and again 4 h after soman exposure. Results: The initial seizure duration, the EEG power integral at 6 h after exposure, and the percentage of rats that developed spontaneous recurrent seizure were reduced in rats treated with cystamine, compared to those that received only midazolam. In addition, cystamine reduced neurodegeneration in seizure-sensitive brain regions following soman exposure, compared to midazolam. Conclusions: Our findings highlight the potential for aminothiols to serve as adjunctive therapy to midazolam in treating cholinergic-induced toxicity and suggest broader applications of aminothiols in neuroprotection and neurological disorders.
Keywords: Organophosphorus nerve agents, Seizures, Status Epilepticus, Cystamine, neuroprotection
Received: 24 Mar 2025; Accepted: 20 May 2025.
Copyright: © 2025 Biney, Schultz, Stone, Nguyen, Wang, De Araujo Furtado and Lumley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lucille Lumley, US Army Medical Research Institute of Chemical Defense, Aberdeen, Maryland, United States
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