AUTHOR=Biney Abiel K. , Schultz Caroline R. , Stone Michael F. , Nguyen Donna A. , Wang Annie , de Araujo Furtado Marcio , Lumley Lucille A. 

TITLE=Cystamine reduces neurodegeneration and epileptogenesis following soman-induced status epilepticus in rats

JOURNAL=Experimental Biology and Medicine

VOLUME=Volume 250 - 2025

YEAR=2025

URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2025.10598

DOI=10.3389/ebm.2025.10598

ISSN=1535-3699

ABSTRACT=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. 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. Midazolam was administered 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. 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. 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.