Evidence map›Paper›PMID 38129129›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2024

Inhibiting Inducible Nitric Oxide Synthase with 1400W Reduces Soman (GD)-Induced Ferroptosis in Long-Term Epilepsy-Associated Neuropathology: Structural and Functional Magnetic Resonance Imaging Correlations with Neurobehavior and Brain Pathology.

Marson Putra, Suraj S Vasanthi, Nikhil S Rao, Christina Meyer, Madison Van Otterloo, Lal Thangi, Daniel R Thedens, Sridhar S Kannurpatti, Thimmasettappa Thippeswamy

Open access · hybridAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
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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

9 authors at 3 institutions in 1 country.

Marson PutraDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Suraj S VasanthiDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Nikhil S RaoDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Christina MeyerDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Madison Van OtterlooDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Lal ThangiDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Daniel R ThedensDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Sridhar S KannurpattiDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.).
Thimmasettappa ThippeswamyDepartment of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.) tswamy@iastate.edu.
Iowa State University · USRutgers, The State University of New Jersey · USUniversity of Iowa · US

Funding

Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
Saracatinib and 1400W Counteract Nerve Agents-Induced Long-Term NeurotoxicityU01NS117284 · NINDS · IOWA STATE UNIVERSITY · PI THIPPESWAMY, THIMMASETTAPPA · 2021 to 2025
$3.9M
NIEHS NIH HHS P30 ES005605NINDS NIH HHS U01 NS117284
6 · The paper itself

Abstract

Organophosphate (OP) nerve agent (OPNA) intoxication leads to long-term brain dysfunctions. The ineffectiveness of current treatments for OPNA intoxication prompts a quest for the investigation of the mechanism and an alternative effective therapeutic approach. Our previous studies on 1400W, a highly selective inducible nitric oxide synthase (iNOS) inhibitor, showed improvement in epilepsy and seizure-induced brain pathology in rat models of kainate and OP intoxication. In this study, magnetic resonance imaging (MRI) modalities, behavioral outcomes, and biomarkers were comprehensively investigated for brain abnormalities following soman (GD) intoxication in a rat model. T1 and T2 MRI robustly identified pathologic microchanges in brain structures associated with GD toxicity, and 1400W suppressed those aberrant alterations. Moreover, functional network reduction was evident in the cortex, hippocampus, and thalamus after GD exposure, and 1400W rescued the losses except in the thalamus. Behavioral tests showed protection by 1400W against GD-induced memory dysfunction, which also correlated with the extent of brain pathology observed in structural and functional MRIs. GD exposure upregulated iron-laden glial cells and ferritin levels in the brain and serum, 1400W decreased ferritin levels in the epileptic foci in the brain but not in the serum. The levels of brain ferritin also correlated with MRI parameters. Further, 1400W mitigated the overproduction of nitroxidative markers after GD exposure. Overall, this study provides direct evidence for the relationships of structural and functional MRI modalities with behavioral and molecular abnormalities following GD exposure and the neuroprotective effect of an iNOS inhibitor, 1400W. SIGNIFICANT STATEMENT: Our studies demonstrate the MRI microchanges in the brain following GD toxicity, which strongly correlate with neurobehavioral performances and iron homeostasis. The inhibition of iNOS with 1400W mitigates GD-induced cognitive decline, iron dysregulation, and aberrant brain MRI findings.

Indexed as

EpilepsyFerroptosisSomanAmidinesAnimalsBenzylaminesBrainEnzyme InhibitorsFerritinsIronMagnetic Resonance ImagingNitric OxideNitric Oxide Synthase Type IIRatsAmidinesBenzylaminesEnzyme InhibitorsFerritinsIronNitric OxideNitric Oxide Synthase Type IISoman

Identifiers

PMID38129129
PMCPMC10801728
OpenAlexW4390047501

What Socratic holds

Textmetadata
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 Socratic graph.