Corticosterone Potentiates DFP-Induced Neuroinflammation and Affects High-Order Diffusion Imaging in a Rat Model of Gulf War Illness

Details

• Personal Author:
  Calderazzo S ; Kelly KA ; Killiany RJ ; Koo B-B ; Michalovicz LT ; O'Callaghan JP ; Sullivan K
• Description:
  Veterans of the 1991 Gulf War were potentially exposed to a variety of toxic chemicals, including sarin nerve agent and pesticides, which have been suspected to be involved in the development of Gulf War Illness (GWI). Several of these exposures cause a neuroinflammatory response in mice, which may serve as a basis for the sickness behavior-like symptoms seen in veterans with GWI. Furthermore, conditions mimicking the physiological stress experienced during the war can exacerbate this effect. While neuroinflammation has been observed post-exposure using animal models, it remains a challenge to evaluate neuroinflammation and its associated cellular and molecular changes in vivo in veterans with GWI. Here, we evaluated neuroimmune-associated alterations in intact brains, applying our existing GWI mouse model to rats, by exposing them to 4 days of corticosterone (CORT; 200 mg/L in the drinking water), to mimic high physiological stress, followed by a single injection of the sarin nerve agent surrogate, diisopropyl fluorophosphate (DFP; 1.5 mg/kg, i.p.). Then, we evaluated the neuroinflammatory responses using qPCR of cytokine mRNA and also examined brain structure with a novel high-order diffusion MRI. We found a CORT-enhancement of DFP-induced neuroinflammation, extending our mouse GWI model to the rat. High order diffusion MRI revealed different patterns among the different treatment groups. Particularly, while the CORT + DFP rats had more restricted spatial patterns in the hippocampus and the hypothalamus, the highest and most wide-spread differences were shown in DFP-treated rats compared to the controls in the thalamus, the amygdala, the piriform cortex and the ventral tegmental area. The association of these diffusion changes with neuroinflammatory cytokine expression indicates the potential for GW-relevant exposures to result in connectivity changes in the brain. By transferring this high order diffusion MRI into in vivo imaging in veterans with GWI, we can achieve further insights on the trajectories of the neuroimmune response over time and its impacts on behavior and potential neurological damage. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Environmental Exposure Hazardous Substances Insecticides Laboratories Men Occupational Health Risk Assessment Risk Factors Safety Women

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• Keywords:
  Author Keywords: Neuroimmune Response Brain Function Cellular Effects Chemical Agents Chemical Properties Chemical Warfare Agents Corticosterone Cytokine Cytokines Diffusion MRI Diisopropyl Fluorophosphate Exposure Levels Gulf War Illness Humans In Vivo Study Laboratory Animals Military Personnel Models Molecular Biology Neuroinflammation Pesticides Physiological Stress Rat Model Risk Factors Toxic Effects Toxins

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• ISSN:
  0889-1591
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  42-46
• Volume:
  67
• NIOSHTIC Number:
  nn:20050837
• Citation:
  Brain Behav Immun 2018 Jan; 67:42-46
• Contact Point Address:
  Bang-Bon Koo, Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118
• Email:
  bbkoo@bu.edu
• CAS Registry Number:
  Diisopropyl fluorophosphate (CAS RN 55-91-4)
• Federal Fiscal Year:
  2018
• Peer Reviewed:
  True
• Source Full Name:
  Brain, Behavior, and Immunity
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:90aeb5cf40e31e923cecee9951aad8a5e5b3b7d8574c434ab76a78aaef210514f1db26db1110ff63a4fc412b9b477ffca9d999a5be6b60199f705e2d5b692d7a
• Download URL:
  https://stacks.cdc.gov/view/cdc/211037/cdc_211037_DS1.pdf
• File Type:
  [PDF - 722.63 KB ]