Nerve Agent Exposure and Physiological Stress Alter Brain Microstructure and Immune Profiles After Inflammatory Challenge in a Long-Term Animal Model of Gulf War Illness (Dataset)

Details

• Personal Author:
  Kelly KA ; Michalovicz LT ; O'Callaghan JP
• Description:
  Gulf War Illness (GWI) is a disorder experienced by one-third of the veterans of the 1990-91 Gulf War, with symptoms including fatigue, chronic pain, respiratory and memory problems. Exposure to toxic chemicals during the war, such as oil well fire smoke, pesticides, physiological stress, and nerve agents, is thought to have triggered abnormal neuroinflammatory responses that contribute to GWI. Previous studies using animal models have indicated that combined exposure to high physiological stress and GW-relevant organophosphates, such as sarin nerve agent and chlorpyrifos and dichlorvos, produces neuroinflammation and changes in diffusion magnetic resonance imaging (MRI) measures, suggesting a neuroimmune basis for GWI. In the current study, we examined brain structure and immune function of a chronic rat model of GWI and showed that a combination of long-term corticosterone treatment (CORT, to mimic high physiological stress) and diisopropyl fluorophosphate exposure (DFP, to mimic sarin exposure) resulted in elevations of multiple inflammatory cytokines, an increased activated microglial population, and disrupted brain microstructure in the hippocampal regions. Moreover, prior exposures to these agents modeling the "in-theater," initiating exposure conditions experienced by veterans with GWI can induce long-term alterations in neuroimmune signaling, resulting in an exacerbated neuroinflammatory response to future immune challenges. The goal of the study was to establish a long-term model of GWI in rats that would be more relevant to the current state of ill veterans. As such, rats were initially exposed to the stress hormone corticosterone (CORT) for 1 week followed by a single exposure to the sarin surrogate diisopropyl fluorophosphate, to mimic "in-theater" conditions of high physiological stress and nerve agent exposure. This initial exposure was followed up with 4 weeks of intermittent re-exposure to week-long bouts of CORT and a final exposure to the prototypical inflammagen, lipopolysaccharide (LPS) to mimic a systemic inflammatory challenge. [Description provided by NIOSH]
• Subjects:
  Biochemistry Immune System Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Biochemical Effects Chronic Inflammation Cytokines Immunochemistry Magnetic Resonance Imaging Military Personnel MRI Neurological Disorders
• DOI:
  https://doi.org/10.26616/NIOSHRD-1105-2024-0
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Dataset
• Genre:
  Research Dataset
• Place as Subject:
  Boston Region [OSHA] ; Massachusetts ; Philadelphia Region [OSHA] ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• NIOSHTIC Number:
  nn:20070504
• Citation:
  Morgantown, WV: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Research Dataset RD-1105-2024-0, 2024 Dec; :dataset
• Contact Point Address:
  NIOSH/HELD Toxicology and Molecular Biology Branch
• Federal Fiscal Year:
  2025
• Peer Reviewed:
  False
• Source Full Name:
  Nerve agent exposure and physiological stress alter brain microstructure and immune profiles after inflammatory challenge in a long-term animal model of Gulf War Illness
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:91b962505cccf9b3e2b6b1186724993dab43bff13e15ea51668e044b92e440182e75d080e5e6a3a1ec4af5f2ec89e0a921dbae936aad628cc6c90c07db47dacb
• Download URL:
  https://stacks.cdc.gov/view/cdc/208702/cdc_208702_DS1.pdf
• File Type:
  [PDF - 100.60 KB ]