Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model
Abstract
Gulf War Illness (GWI) is a multi-symptom disorder with features characteristic of "sickness" behavior, including cognitive impairment, fatigue, depression, sleep disruption, and gastrointestinal and dermatological problems. Sickness behavior, a normal manifestation of an inflammatory response due to infection or injury, resolves when homeostasis is restored, but in GWI the symptoms persist, findings suggestive of a heightened or chronic neuroimmune/neuroinflammatory disorder. The expression of proinflammatory cytokines and chemokines are the basis of sickness behavior and are the key elements of inflammation. Notably, low-level inhalation exposure of experimental animals to sarin, the nerve agent implicated in GWI, causes neuroinflammation. Further, the sarin surrogate diisopropyl phosphorofluoridate (DFP), increases proinflammatory cytokine expression in multiple brain regions. Finally, the stress of the war theater may have affected the blood brain barrier, allowing GWI-relevant agents access to the CNS. A role for stress in GWI is bolstered by our finding of increased proinflammatory cytokine expression in brain when DFP was preceded by a week of treatment with the rodent-specific stress hormone, corticosterone (CORT). The above suggest a possible critical and unrecognized link between the stressful environment of the Gulf War theater, agent exposures unique to this war, and a resulting adverse heightened neuroinflammatory outcome. Our overarching hypothesis is that exposure to GWI-relevant compounds leads to enhanced and/or prolonged expression of proinflammatory mediators in the brain. Our data also lead us to hypothesize that brief high physiological levels of the stress hormone, cortisol, greatly exacerbate the effects of GWI-related exposures and that the FDA-approved anti-inflammatory, minocycline, can ameliorate heightened neuroinflammation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2011
- Accession Number
- ADA554742
Entities
People
- Diane B. Miller
- James P. O'Callaghan
- Stephen M. Lasley
Organizations
- University of Illinois at Chicago