Evidence map›Paper›PMID 42190906›Full record

ArticleNeuropharmacology2026

Comprehensive evaluation of neurosteroid monotherapy and neurosteroid-midazolam combination therapy in mitigating the nerve agent soman-induced chronic neuropsychiatric dysfunction, epileptogenesis, neuroinflammation and neurodegeneration in pediatric models.

Steve D Reddy, Sreevidhya Ramakrishnan, Tanveer Singh, Xin Wu, Doodipala Samba Reddy

Abstract read
In one paragraph

Article in Neuropharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Steve D ReddyDepartment of Neuroscience and Experimental Therapeutics, Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX, USA.
Sreevidhya RamakrishnanDepartment of Neuroscience and Experimental Therapeutics, Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Tanveer SinghDepartment of Neuroscience and Experimental Therapeutics, Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Xin WuDepartment of Neuroscience and Experimental Therapeutics, Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Doodipala Samba ReddyDepartment of Neuroscience and Experimental Therapeutics, Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX, USA; Institute of Pharmacology and Neurotherapeutics, Texas A&M University Health Science Center, Bryan, TX, USA. Electronic address: sambareddy@tamu.edu.

Funding

Novel pediatric anticonvulsants for nerve agentsU01NS117209 · NINDS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI REDDY, DOODIPALA SAMBA · 2020 to 2024
$3.7M
Novel Water-Soluble Adjunct Anticonvulsants for Nerve AgentsU01NS117278 · NINDS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI REDDY, DOODIPALA SAMBA · 2020 to 2022
$1.3M
Novel Anticonvulsants for Nerve Agents and Refractory Status EpilepticusUG3NS138911 · NINDS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI Doodipala Samba Reddy · 2025 to 2026
$1.1M
NINDS NIH HHS U01 NS117209NINDS NIH HHS U01 NS117278NINDS NIH HHS UG3 NS138911
6 · The paper itself

Abstract

Children are especially vulnerable to the neurotoxic effects of nerve agents, which can cause lasting neuronal dysfunction, including cognitive impairments, epilepsy, and related comorbidities. Current benzodiazepine anticonvulsants often fail to prevent long-term neuropathology following neurotoxic chemical exposure, underscoring the urgent need for more effective treatments. This study investigated the therapeutic potential of the synthetic neurosteroid ganaxolone (GX) in a pediatric rat model of the nerve agent soman exposure. Pediatric (postnatal day 21) rats were acutely exposed to soman and received GX alone or in combination with midazolam treatment 40 min later. Continuous video-EEG monitoring, behavioral assessments and MRI imaging were conducted over a 3-month period after the acute challenge. Soman exposure led to persistent epileptic seizures, electrographic ictal biomarkers, cognitive dysfunction, behavioral impairments, hippocampal atrophy, neuroinflammation and neurodegeneration. Midazolam alone had minimal neuroprotective effects. In both monotherapy and combination regimen, GX significantly reduced memory deficits, anxiety, and depressive-like behaviors. GX attenuated spontaneous seizures and suppressed non-convulsive epileptiform discharges, interictal spikes, and high-frequency oscillations, suggesting disease-modifying effects. Mechanistic immunohistology analyses showed that GX preserved parvalbumin-positive inhibitory interneurons and NeuN-positive principal neurons, enhanced doublecortin-positive neurogenesis in the hippocampus, and reduced inflammatory microgliosis as indicated by IBA1 expression. MRI scans confirmed reduced neuropathological changes in GX-treated animals. Collectively, these findings demonstrate that GX alone or in combination with midazolam offers strong neuroprotective, antiepileptogenic, and anti-inflammatory benefits, highlighting its promise as a robust pediatric anticonvulsant for nerve agent-induced seizures and long-term neurologic dysfunction.

Indexed as

AnticonvulsantsEpilepsyMidazolamNeuroinflammatory DiseasesNeurosteroidsPregnanoloneSomanAnimalsDisease Models, AnimalDrug Therapy, CombinationHippocampusMaleNerve AgentsRatsRats, Sprague-DawleyAnticonvulsantsganaxoloneMidazolamNerve AgentsNeurosteroidsPregnanoloneSomanEpilepsyEpileptogenesisNerve agentNeuroinflammationPediatricSoman

Identifiers

PMID42190906
PMCPMC13340581

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.