Sex based structural and functional MRI outcomes in the rat brain after soman (GD) exposure induced status epilepticus

Meghan Gage; Suraj S Vasanthi; Christina M Meyer; Nikhil S Rao; Daniel R Thedens; Sridhar S Kannurpatti; Thimmasettappa Thippeswamy

doi:10.1002/epi4.12701

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Sex based structural and functional MRI outcomes in the rat brain after soman (GD) exposure induced status epilepticus

Journal article

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Sex based structural and functional MRI outcomes in the rat brain after soman (GD) exposure induced status epilepticus

Meghan Gage, Suraj S Vasanthi, Christina M Meyer, Nikhil S Rao, Daniel R Thedens, Sridhar S Kannurpatti and Thimmasettappa Thippeswamy

Epilepsia open, Vol.8(2), pp.399-410

06/2023

DOI: 10.1002/epi4.12701

PMCID: PMC10235578

PMID: 36718979

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Abstract

Exposure to the nerve agent, soman (GD), induces status epilepticus (SE), epileptogenesis and even death. Although rodent models studying the pathophysiological mechanisms show females to be more reactive to soman, no tangible sex differences in brains post-exposure have been reported. In this study, we used multimodal imaging using MRI in adult rats to determine potential sex-based biomarkers of soman effects. Male and female Sprague Dawley rats were challenged with 1.2xLD soman followed by medical countermeasures. Ten weeks later the brains were analyzed via structural and functional MRI. Despite no significant sex differences in the initial SE severity after soman exposure, long-term MRI-based structural and functional differences were evident in the brains of both sexes. While T2 MRI showed lesser soman-induced neurodegeneration, large areas of T1 enhancements occurred in females than males, indicating a distinct pathophysiology unrelated to neurodegeneration. fMRI-based resting-state functional connectivity (RSFC), indicated greater reductions in soman-exposed females than males, associating with the T1 enhancements (unrelated to neurodegeneration) rather than T2-hyperintensity or T1-hypointensity (representing neurodegeneration). The wider T1 enhancements associating with the decreased spontaneous neuronal activity in multiple resting state networks in soman-exposed females than males suggest that neural changes unrelated to cellular atrophy impinge on brain function post-exposure. Taken together with lower spontaneous neural activity in soman exposed females, the results indicate some form of neuroprotective state that was not present in males. The results indicate that endpoints other than neurodegeneration may need to be considered to translate sex-based nerve agent effects in humans.

Epilepsy

status epilepticus

nerve agent

neurodegeneration

MRI resting state

Details

Title: Subtitle: Sex based structural and functional MRI outcomes in the rat brain after soman (GD) exposure induced status epilepticus
Creators: Meghan Gage - Iowa State University
Suraj S Vasanthi - Iowa State University
Christina M Meyer - Iowa State University
Nikhil S Rao - Iowa State University
Daniel R Thedens - University of Iowa
Sridhar S Kannurpatti - Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, NJ, United States
Thimmasettappa Thippeswamy - Iowa State University
Resource Type: Journal article
Publication Details: Epilepsia open, Vol.8(2), pp.399-410
DOI: 10.1002/epi4.12701
PMID: 36718979
PMCID: PMC10235578
NLM abbreviation: Epilepsia Open
ISSN: 2470-9239
Grant note: DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: U01NS117284
Language: English
Electronic publication date: 01/31/2023
Date published: 06/2023
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering
Record Identifier: 9984363655402771

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