Evidence map›Paper›PMID 40022508›Full record

ArticleCNS neuroscience & therapeutics2025

Allopregnanolone as an Adjunct Therapy to Midazolam is More Effective Than Midazolam Alone in Suppressing Soman-Induced Status Epilepticus in Male Rats.

Peter M Andrew, Jeremy A MacMahon, Xiuzhen Liu, Naomi H Saito, Kyle E Berger, Julia E Morgan, Ashish Dhir, Danielle J Harvey, Hilary S McCarren, Michael A Rogawski and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

11 authors.

Peter M AndrewDepartment of Molecular Biosciences, University of California, Davis, Davis, California, USA.
Jeremy A MacMahonDepartment of Molecular Biosciences, University of California, Davis, Davis, California, USA.
Xiuzhen LiuDepartment of Molecular Biosciences, University of California, Davis, Davis, California, USA.
Naomi H SaitoDepartment of Public Health Sciences, School of Medicine, University of California, Davis, Davis, California, USA.
Kyle E BergerNeuroscience Department, Medical Toxicology Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen, Maryland, USA.
Julia E MorganNeuroscience Department, Medical Toxicology Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen, Maryland, USA.
Ashish DhirDepartment of Neurology, School of Medicine, University of California, Davis, Sacramento, California, USA.
Danielle J HarveyDepartment of Public Health Sciences, School of Medicine, University of California, Davis, Davis, California, USA.
Hilary S McCarrenNeuroscience Department, Medical Toxicology Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen, Maryland, USA.
Michael A RogawskiDepartment of Neurology, School of Medicine, University of California, Davis, Sacramento, California, USA.ORCID 0000-0002-3296-8193
Pamela J LeinDepartment of Molecular Biosciences, University of California, Davis, Davis, California, USA.ORCID 0000-0001-7665-7584

Funding

Training and Education CoreU54NS079202 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEIN, PAMELA J · 2012 to 2021
$35.7M
UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate IntoxicationU54NS127758 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Pamela J Lein · 2022 to 2026
$17.2M
Research Project: Pathologic Significance of Maternal AutoantibodiesP50HD103526 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEONARD J. ABBEDUTO, Melissa Dawn Bauman · 2020 to 2026
$9.7M
NICHD NIH HHS P50 HD103526NINDS NIH HHS U54 NS079202NINDS NIH HHS U54 NS127758U.S. Department of Energy DE-SC0014664
6 · The paper itself

Abstract

aimsHumans and animals acutely intoxicated with the organophosphate soman can develop sustained status epilepticus (SE) that rapidly becomes refractory to benzodiazepines. We compared the antiseizure efficacy of midazolam, a current standard of care treatment for OP-induced SE, versus combined therapy with midazolam and allopregnanolone (ALLO) in a rat model of soman-induced SE.

methodsSoman-intoxicated male rats with robust seizure behavior and high-amplitude electroencephalographic (EEG) activity were administered midazolam (0.65 mg, i.m.) 20 min after seizure initiation and 10 min later either a second dose of midazolam or ALLO (12 or 24 mg/kg, i.m.). Seizure behavior and EEG were monitored for 4 h after treatment. Brains were collected at the end of the monitoring period for histological analyses.

resultsAnimals receiving 2 doses of midazolam exhibited persistent SE. Sequential dosing with midazolam followed by ALLO suppressed electrographic seizure activity. The combination therapy also significantly reduced soman-induced neurodegeneration and neuroinflammation compared to 2 doses of midazolam. High but not low dose ALLO was associated with transitory and reversible respiratory compromise during the 1 h period after dosing.

conclusionsTreatment with midazolam followed by ALLO was more effective than 2 doses of midazolam in suppressing benzodiazepine-refractory, soman-induced SE, and in mitigating its acute neuropathological consequences.

Indexed as

AnticonvulsantsMidazolamPregnanoloneSomanStatus EpilepticusAnimalsBrainDisease Models, AnimalDose-Response Relationship, DrugDrug Therapy, CombinationElectroencephalographyMaleRatsRats, Sprague-DawleyAnticonvulsantsMidazolamPregnanoloneSomanbenzodiazepinechemical threat agentsneurosteroidorganophosphatepolytherapyseizure

Identifiers

PMID40022508
PMCPMC11871396

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.