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Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans.
Neurotoxicol Teratol. 2018 Jul - Aug; 68:36-46.NT

Abstract

In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 ± 7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein ε4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R2 = 0.215, standardized coefficient β = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus.

Authors+Show Affiliations

Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States; Department of Psychiatry, University of California San Francisco, San Francisco, CA, United States. Electronic address: linda.chao@ucsf.edu.Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

29733897

Citation

Chao, Linda L., and Yu Zhang. "Effects of Low-level Sarin and Cyclosarin Exposure On Hippocampal Microstructure in Gulf War Veterans." Neurotoxicology and Teratology, vol. 68, 2018, pp. 36-46.
Chao LL, Zhang Y. Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans. Neurotoxicol Teratol. 2018;68:36-46.
Chao, L. L., & Zhang, Y. (2018). Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans. Neurotoxicology and Teratology, 68, 36-46. https://doi.org/10.1016/j.ntt.2018.05.001
Chao LL, Zhang Y. Effects of Low-level Sarin and Cyclosarin Exposure On Hippocampal Microstructure in Gulf War Veterans. Neurotoxicol Teratol. 2018 Jul - Aug;68:36-46. PubMed PMID: 29733897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans. AU - Chao,Linda L, AU - Zhang,Yu, Y1 - 2018/05/04/ PY - 2017/12/07/received PY - 2018/04/13/revised PY - 2018/05/02/accepted PY - 2018/5/8/pubmed PY - 2019/10/28/medline PY - 2018/5/8/entrez KW - Chemical warfare agents KW - Diffusion tensor imaging KW - Diffusivity KW - Gulf War KW - Hippocampus KW - Organophosphate SP - 36 EP - 46 JF - Neurotoxicology and teratology JO - Neurotoxicol Teratol VL - 68 N2 - In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 ± 7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein ε4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R2 = 0.215, standardized coefficient β = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus. SN - 1872-9738 UR - https://www.unboundmedicine.com/medline/citation/29733897/Effects_of_low_level_sarin_and_cyclosarin_exposure_on_hippocampal_microstructure_in_Gulf_War_Veterans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0892-0362(17)30245-3 DB - PRIME DP - Unbound Medicine ER -