Evidence map›Paper›PMID 28329845›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2017

Editor's Highlight: Spatiotemporal Progression and Remission of Lesions in the Rat Brain Following Acute Intoxication With Diisopropylfluorophosphate.

Sílvia Sisó, Brad A Hobson, Danielle J Harvey, Donald A Bruun, Douglas J Rowland, Joel R Garbow, Pamela J Lein

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
13.2field-weighted citation impact, top 2% of its field
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

44 citing papers in PubMed, 54 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Sílvia SisóTranslational Biology in the Department of Research, BioMarin Pharmaceuticals Inc, Novato, California, USA.
Brad A HobsonDepartment of Molecular Biosciences School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Danielle J HarveyDepartment of Public Health Sciences School of Medicine, University of California-Davis, Davis, California, USA.
Donald A BruunDepartment of Molecular Biosciences School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Douglas J RowlandDepartment of Biomedical Engineering and the Center for Molecular and Genomic Imaging College of Engineering, University of California-Davis, Davis, California, USA.
Joel R GarbowBiomedical Magnetic Resonance Laboratory, Mallinckrodt Institute of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
Pamela J LeinDepartment of Molecular Biosciences School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
BioMarin (United States) · USUniversity of California, Davis · USWashington University in St. Louis · US

Funding

Training and Education CoreU54NS079202 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ROGAWSKI, MICHAEL A. · 2012 to 2021
$35.7M
Predoctoral Training in Pharmacological SciencesT32GM099608 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HELL, JOHANNES W · 2012 to 2021
$2.2M
NIGMS NIH HHS T32 GM099608NINDS NIH HHS U54 NS079202
6 · The paper itself

Abstract

Similar to organophosphate (OP) nerve agents, diisopropylfluorophosphate (DFP) rapidly and irreversibly inhibits acetylcholinesterase, leading to convulsions that can progress to status epilepticus (SE). However, in contrast to the OP nerve agents, the long-term consequences of DFP-induced SE are not well known. Thus, we characterized the spatiotemporal profile of neuropathology during the first 2 months following acute DFP intoxication. Adult, male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30 min prior to successive administration of DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im), and 2-pralidoxime (25 mg/kg, im), exhibited moderate-to-severe seizure behavior, yet survived until euthanized at 0.5 to 60 days post exposure. Analyses of brains and hearts stained with hematoxylin-eosin, or of brains immunostained for neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), or ionized binding adapter molecule 1 (IBA1), revealed progressive neuronal cell death, neuroinflammation, and tissue remodeling across limbic brain regions and the cerebral cortex, with no detectable pathology in the cerebellum or the heart. The lesion type and progression varied according to brain region and time after exposure. Across multiple brain regions, neuronal necrosis peaked after the first week, and neuroinflammation persisted at least 2 months after intoxication. Notably, mineralization was observed at later times in the thalamus, and to a more limited extent, in the hippocampus. Lesion severity was influenced by the initial seizure severity, and spontaneous recurrent seizures were associated with more severe brain damage. These findings parallel descriptions of neuropathology in preclinical models of acute intoxication with OP nerve agents, and other seizurogenic chemicals, suggesting conserved mechanisms of pathology downstream of chemical-induced SE.

Indexed as

AnimalsBehavior, AnimalBrainCell DeathCholinesterase InhibitorsIsoflurophateMaleNecrosisNeuronsNeurotoxicity SyndromesRats, Sprague-DawleySeverity of Illness IndexSpatio-Temporal AnalysisStatus EpilepticusTime FactorsCholinesterase InhibitorsIsoflurophatehistopathologyneurodegenerationneuroinflammationorganophosphate neurotoxicity

Identifiers

PMID28329845
PMCPMC6070115
OpenAlexW2594142886

What OpenQuestion holds

Textmetadata
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.