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

Details

• Personal Author:
  Cheng C-H ; Chiplunkar VP ; Guan Y ; Kelly KA ; Koo B-B ; Medalla ML ; Michalovicz LT ; Mortazavi F ; O'Callaghan JP ; Sullivan K
• Description:
  Gulf War Illness (GWI) is a disorder experienced by many veterans of the 1991 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 have examined the acute effects of combined physiological stress and chemical exposures using GWI rodent models and presented findings related to neuroinflammation and changes in diffusion magnetic resonance imaging (MRI) measures, suggesting a neuroimmune basis for GWI. In the current study, using ex vivo MRI, cytokine mRNA expression, and immunohistological analyses of brain tissues, we examined the brain structure and immune function of a chronic rat model of GWI. Our data showed that a combination of long-term corticosterone treatment (to mimic high physiological stress) and diisopropyl fluorophosphate exposure (to mimic sarin exposure) primed the response to subsequent systemic immune challenge with lipopolysaccharide resulting in elevations of multiple cytokine mRNAs, an increased activated glial population, and disrupted brain microstructure in the cingulate cortex and hippocampus compared to control groups. Our findings support the critical role of neuroinflammation, dysregulated glial activation, and their relationship to disrupted brain microstructural integrity in the pathophysiology of GWI and highlight the unique consequences of long-term combined exposures on brain biochemistry and structural connectivity. [Description provided by NIOSH]
• Subjects:
  Biochemistry Immune System Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Author Keywords: Gulf War Illness Biochemical Effects Chronic Inflammation CORT Cytokines DFP Diffusion MRI Glial Activation Immunochemistry Magnetic Resonance Imaging Military Personnel MRI Neuroinflammation Neurological Disorders

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• ISSN:
  2666-3546
• Document Type:
  Text
• Genre:
  Journal Article
• 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
• Volume:
  42
• NIOSHTIC Number:
  nn:20070195
• Citation:
  Brain Behav Immun Health 2024 Dec; 42:100878
• Contact Point Address:
  Lindsay T. Michalovicz, Health Effects Laboratory Division, Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health, 1000 Frederick Ln, M/S L3014, Morgantown, WV, 26508, USA
• Email:
  yqp4@cdc.gov
• Federal Fiscal Year:
  2025
• Peer Reviewed:
  True
• Source Full Name:
  Brain, Behavior, & Immunity - Health
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:73a2915bcd28c466c5e542cf565c2bca3fdafc32b907a2c77cbe8b5529ed17cfb51cb7397fe897ded667cd3fd0f2ab75e83ce9cb891f9c9fe09ef891ca843921
• Download URL:
  https://stacks.cdc.gov/view/cdc/208452/cdc_208452_DS1.pdf
• File Type:
  [PDF - 2.96 MB ]