Neurosteroid Mitigation of Long-term Neuropsychiatric Outcomes in Pediatric Nerve Agent Neurotoxicity
Abstract number :
2.326
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2025
Submission ID :
480
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Michael Neff, BS – Texas A&M University College of Medicine
Sreevidhya Ramakrishnan, PhD – Texas A&M University College of Medicine
Xin Wu, MD – Texas A&M University College of Medicine
D. Samba Reddy, PhD, RPh – Texas A&M University College of Medicine
Rationale: Adolescents are at an increased risk to the long-term neurotoxic effects of nerve agents. Exposure in a pediatric population leads to a progressive multifactorial sequela that includes cognitive impairment and developmental disabilities. However, there are few therapeutic interventions to prevent the long-term consequences of nerve agent exposure on pediatric population. In this study, we investigated the long-term developmental impact of pediatric exposure to the nerve agent soman (GD) and the use of the synthetic neurosteroid ganaxolone (GX) as a potential neurotherapeutic intervention.
Methods: Pediatric rats (P28) were exposed to GD via SC injection and treated 40 minutes after exposure with either midazolam (MDZ) alone, MDZ+ GX, or GX alone. Control group animals were age-matched unexposed controls. Animals were then allowed to mature into adulthood and were evaluated 1 month, 3 months, and 10 months post exposure in a wide array of cognitive, behavioral, depression and behavior tests.
Results: GD exposed animals displayed increased aggressive traits, deficits in object recognition memory, mood, and sociability compared to naïve animals. Exposed animals showed progressive behavioral and cognitive deterioration that correlated with development into adulthood. GX post-exposure treatment alone or adjunctive with MDZ showed significantly increased attenuation of all deficits compared to MDZ monotherapy.
Conclusions: This pediatric model replicates the long-term developmental and cognitive dysfunction associated with nerve agent exposure, while neurosteroid intervention demonstrated significant neuroprotection against these sequelae.
Funding: NIH Grant U01-NS117209 (to D.S.R.)
Anti-seizure Medications