Browsing by Subject "Persian Gulf Syndrome"

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    A common language for Gulf War Illness (GWI) research studies: GWI common data elements
    (Elsevier, 2022) Cohen, Devra E.; Sullivan, Kimberly A.; McNeil, Rebecca B.; Gulf War Illness Common Data Elements Working Group; Symptoms Assessment Working Group; McNeil, Rebecca B.; Ashford, Wes; Bested, Alison; Bunker, James; Cheema, Amanpreet; Cohen, Devra E.; Cook, Dane; Cournoyer, Jeffrey; Craddock, Travis; Golier, Julia; Hardie, Anthony; Helmer, Drew; Lindheimer, Jacob B.; Janulewicz Lloyd, Patricia; Kerr, Kathleen; Krengel, Maxine; Nadkarni, Shree; Nugent, Shannon; Paris, Bonnie; Reinhard, Matthew; Rumm, Peter; Schneiderman, Aaron; Sims, Kellie J.; Steele, Lea; Turner, Marsha; Systems Assessment Working Group; Sullivan, Kimberly A.; Abdullah, Laila; Abreu, Maria; Abu-Donia, Mohamed; Aenlle, Kristina; Arocho, Jimmy; Balbin, Elizabeth; Baraniuk, James; Block, Karen; Block, Michelle; DeBeer, Bryann; Engdahl, Brian; Filipov, Nikolay; Fletcher, Mary Ann; Kalasinsky, Victor; Kokkotou, Efi; Lidie, Kristy; Little, Deborah; Loging, William; Morris, Marianna; Nathanson, Lubov; Nichols, Montra Denise; Pasinetti, Giulio; Shungu, Dikoma; Waziry, Paula; VanLeeuwen, Jon; Younger, Jarred; Pharmacology and Toxicology, School of Medicine
    Aims: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community. Main methods: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments. Key findings: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses. Significance: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing.
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    Circulating HMGB1 is elevated in veterans with Gulf War Illness and triggers the persistent pro-inflammatory microglia phenotype in male C57Bl/6J mice
    (Springer Nature, 2021-07-12) Garza-Lombó, Carla; Thang, Morrent; Greve, Hendrik J.; Mumaw, Christen L.; Messenger, Evan J.; Ahmed, Chandrama; Quinn, Emily; Sullivan, Kimberly; Block, Michelle L.; Pharmacology and Toxicology, School of Medicine
    Gulf War Illness (GWI) is a chronic, multi-symptom peripheral and CNS condition with persistent microglial dysregulation, but the mechanisms driving the continuous neuroimmune pathology are poorly understood. The alarmin HMGB1 is an autocrine and paracrine pro-inflammatory signal, but the role of circulating HMGB1 in persistent neuroinflammation and GWI remains largely unknown. Using the LPS model of the persistent microglial pro-inflammatory response, male C57Bl/6J mice injected with LPS (5 mg/kg IP) exhibited persistent changes in microglia morphology and elevated pro-inflammatory markers in the hippocampus, cortex, and midbrain 7 days after LPS injection, while the peripheral immune response had resolved. Ex vivo serum analysis revealed an augmented pro-inflammatory response to LPS when microglia cells were cultured with the 7-day LPS serum, indicating the presence of bioactive circulating factors that prime the microglial pro-inflammatory response. Elevated circulating HMGB1 levels were identified in the mouse serum 7 days after LPS administration and in the serum of veterans with GWI. Tail vein injection of rHMGB1 in male C57Bl/6 J mice elevated TNFα mRNA levels in the liver, hippocampus, and cortex, demonstrating HMGB1-induced peripheral and CNS effects. Microglia isolated at 7 days after LPS injection revealed a unique transcriptional profile of 17 genes when compared to the acute 3 H LPS response, 6 of which were also upregulated in the midbrain by rHMGB1, highlighting a distinct signature of the persistent pro-inflammatory microglia phenotype. These findings indicate that circulating HMGB1 is elevated in GWI, regulates the microglial neuroimmune response, and drives chronic neuroinflammation that persists long after the initial instigating peripheral stimulus.