Recent research has shed light on the long-term consequences of exposure to organophosphate nerve agents, particularly soman, highlighting their substantial risks for neurological health. Organophosphate nerve agents, including soman (GD), disrupt key neurochemical signals by inhibiting the enzyme acetylcholinesterase. Even though acute treatment can manage immediate symptoms like seizures and respiratory failure, the enduring repercussions—especially chronic neuroinflammation and systemic toxicity—remain poorly understood. This study utilized adult male and female Sprague Dawley rats to explore the lasting effects of acute soman exposure on both neurobehavioral outcomes and physiological markers.
The investigation commenced by administering soman to the rats at a dose of 132 µg/kg, approximately 1.2 times the lethal dose, before initiating treatments to control peripheral cholinergic effects. These included the administration of atropine sulfate and oxime HI-6 to mitigate acute symptoms and midazolam, provided one hour post-exposure, to manage seizures. The study monitored animals extensively following exposure, employing video electroencephalogram (vEEG) technology alongside behavioral assessments.
Notably, the researchers discovered significant neurological shifts at 4–8 weeks post-exposure, with soman-exposed rats demonstrably exhibiting epilepsy-like symptoms confirmed by EEG evidence of spontaneously recurring seizures (SRS). These findings were echoed during behavioral evaluations, wherein significant deficits were noted, particularly memory impairments. The data indicated soman's long-term impact on cognitive function, emphasizing the need for effective monitoring of potential neurological impairments post-exposure.
At the 18-week mark, the study assessed inflammatory markers, signaling chronic neuroinflammation, alongside kidney and liver function indicators. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6, IL-18) showed marked elevation across serum and cerebrospinal fluid (CSF) samples, corroborated by elevated gene expression levels. These findings notify the scientific community concerning the systemic effects of soman, indicating significant connections between neuroinflammation and organ dysfunction.
Surprisingly, hematological parameters did not exhibit substantial changes post-exposure, yet increases were observed in total bilirubin and blood urea nitrogen (BUN) levels. These outcomes hinted at potential liver and kidney dysfunction, reinforcing the relevance of monitoring these biomarkers to track chronic organ impact post-exposure. Importantly, histological evaluations revealed no acute morphological changes within the liver or kidney tissues, contributing to the hypothesis of functional impairments occurring prior to observable structural damage.
The findings from this study highlight the complex interplay between acute nerve agent exposure and its chronic ramifications on health, contributing significantly to the field of chemical warfare medicine. The peripheral markers detected provide insight not only for potential therapeutic measures but also for enhancing diagnostic approaches to manage and support survivors of nerve agent exposure.
Moving forward, these results underline the imperative for developing targeted therapeutic interventions focusing on chronic toxicity markers following soman exposure. These endeavors can greatly assist medical professionals and researchers equipped to tackle the challenges posed by nerve agent-related health crises, fostering more comprehensive recovery frameworks aimed at those affected.