Clarifying the Role Played by Microglia and Astrocyte Activation in Veterans with Gulf War Illness Using Positron Emission Tomography (PET)
Abstract
Gulf War Illness (GWI) is a chronic debilitating disorder characterized by a wide range of symptoms including fatigue, joint pain, memory and concentration problems, headaches, and gastrointestinal problems. It is thought to affect approximately 30% of the 697,000 Veterans who served in the 1991 Gulf War. Despite significant research over the years, GWI remains a disorder primarily diagnosed by self-report of symptoms, making clear diagnosis, treatment, development, and access to benefits and care difficult for many GW Veterans. However, our recent research and that of others have shown important preliminary evidence for objective brain imaging and blood markers that have been associated with the chronic symptoms of GWI. The brain is made up of neurons and glial cells. The glial cells serve a number of functions in the brain. Importantly for this application, they take part in the cascade of events the body puts in motion in response to injury or exposure to toxins. We often refer to this as the neuroinflammatory response. A characteristic of the neuroinflammatory response in some individuals is that the body can over-respond and this then becomes harmful to the individual. A mild example of this type of over-response by the immune system is an allergy where what seems to be a benign event triggers a major response by the body and often some form of treatment is needed. Our research group has taken a team approach to finding a way to solve the mystery of GWI, and one of the concepts we are exploring is the role of neuroinflammation in this illness. As a part of a prior project called the Boston Gulf War Illness Consortium (GWIC), we collected information from a relatively large sample of Veterans with GWI and healthy control Veterans. One very important item that we were able to collect is a blood sample. From this, we were able to measure the concentration of a compound called cytokines. While cytokines have many roles in the body, they can serve to some extent as a marker for neuroinflammation. We have found relationships with a number of symptoms of GWI and the cytokines that we measured. Further, as a part of the GWIC we were able to conduct a small number of positron emission tomography (PET) scans on Veterans with GWI. In a PET scan, a radioactively labeled chemical is injected into the body. This chemical binds to a target agent and the PET scanner detect where the chemical has accumulated. As a part of the GWIC study, we used a chemical that binds to activated microglial cells. Microglial cells are one form of glial cells that form the neuroinflammatory response (become activated). We found higher levels of activated microglial cells in some regions of the brain of Veterans with GWI compared to healthy control Veterans. In this project, we are proposing to extend our prior findings by now looking to see if there are higher concentrations of active astrocytes in the brains of Veterans with GWI compared to healthy control Veterans. Astrocytes are another form of glial cell that form the neuroinflammatory response (become activated). It is important for us to know if the neuroinflammatory response in Veterans with GWI is a generalized response by multiple forms of glial cells or if it is a specific response by one type of glial cells. This information will be essential in planning for effective treatment trials. Finally, in this project we plan to test whether a commonly available form of PET scan chemical can be used as a marker of neuroinflammation in Veterans with GWI. This is important because the chemical we have used in our prior study (part of the GWIC) where we found higher levels of microglia and the chemical we are planning to use in this study to look at astrocytes are not readily available for others to use. Rather, we’ve had to pair with experts at Massachusetts General Hospital who routinely make chemicals of this nature for use in research studies. To look at the transla
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910765
Entities
People
- Ronald Killiany
Organizations
- Boston University Medical Campus
- United States Army