Neurosteroid Treatment Mitigates Persistent Neuroinflammation and Neuronal Damage in a Pediatric Model of Nerve Agent Exposure and Status Epilepticus
Abstract number :
3.342
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2025
Submission ID :
467
Source :
www.aesnet.org
Presentation date :
12/8/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Xin Wu, MD – Texas A&M University College of Medicine
Michael Neff, BS – Texas A&M University College of Medicine
Sreevidhya Ramakrishnan, PhD – Texas A&M University College of Medicine
D. Samba Reddy, PhD, RPh – Texas A&M University College of Medicine
Rationale:
Children are highly susceptible to seizures, status epilepticus (SE) and neurotoxic effects of the nerve agents, which can lead to developmental defects, epilepsy, and chronic neurological dysfunction. There is a great need for new anticonvulsants for the pediatric population. This study tested the effectiveness of the synthetic neurosteroid ganaxolone (GX) on the long-term consequences of soman exposure and status epilepticus in pediatric rats.Methods:
Pediatric rats at postnatal day 28 (P28) were exposed to soman and SE and were treated with GX 40 minutes after exposure. Control group received midazolam alone. MRI scans and histological analyses were conducted 12 months later to assess the long-term neuropathological outcomes.Results:
The soman-exposed rats treated exhibited significant hippocampal atrophy, neuronal loss, and reduced hippocampal volume, suggesting severe damage. However, their T2 relaxation times were similar to control group, indicating limited scarring and changes in fluid density despite the volume reduction. In contrast, they showed considerable enlargement of the lateral ventricles and increased T2 times, indicating fluid expansion. Neuronal lesions observed in MRI scans correlated with histological markers of neurodegeneration and neuroinflammation in control and GX groups. Treatment with GX effectively reduced the loss of principal neurons and interneurons and also decreased the extent of IBA1(+) microgliosis and GFAP(+) astrogliosis, indicating reduction in neuroinflammation. Conclusions:
The findings confirm the long-term neuroprotective effects of GX in mitigating neuroinflammation and neurodegeneration in a pediatric model of soman-induced SE. Funding:
NIH Grant U01-NS117209 (to D.S.R.).
Anti-seizure Medications