Reducing Gulf War-Induced Neurodegeneration by Modulation of Neuroinflammatory Pathways
Abstract
Overarching Challenges: The Department of Defense’s interests in a revolutionary treatment with minimal side effects is a target for this investigation. The challenge to eliminate Gulf War Illness health problems and identify new treatment strategies is fully in line with this proposal’s plan to define the effectiveness of a treatment that, although it has proved beneficial in other neurodegenerative systems, has not yet been tested against Gulf War Illness. Scientific Objective and Rationale: We will test our hypothesis that a traditional medicine, specifically a treatment derived from an extract from the Withania somnifera root, will improve outcomes. This is based on numerous scientific studies modeling other conditions involving neurodegeneration where this extract has proven to be beneficial. The use of this specific extract has not produced detrimental side effects. The first clues of the potential use of this extract against neurodegeneration came from traditional medicine where it was first discovered to be beneficial for neurological symptoms and then followed by laboratory investigations more recently. Treatments that were derived from natural products are plentiful and include aspirin (present in willow bark and noted by Hippocrates) and antimalarial quinine (derived from another tree bark). We hope that the W. sominifera root extract will yield an effective treatment for at least the neurodegenerative aspects of Gulf War Illness. Applicability: The significant and important percentage of Service personnel with Gulf War Illness, after deployment in the Persian Gulf and their exposure to unusual combinations of toxicants, makes it imperative that we find a useful treatment for the resultant health problems. We will apply our long-term expertise studying treatments important to the health of neurons in the central nervous system to this disorder. It is a responsibility of the neuroscience field to rapidly develop therapeutic approaches that will benefit those afflicted as soon as possible. We will test a possible treatment investigating functional outcomes, measured by behavioral testing of our Gulf War model system, and also evaluate changes in the shapes and sizes of nerve cells and related cells in the brain that can be affected by the toxicant exposure and, hopefully, find improvements after the treatment. These changes in architecture can be involved in cognitive difficulties. Finally, there are factors, important to the health of nerve cells in the brain, that we will evaluate for toxicant and treatment-induced changes. We will see whether there are sex differences in the effects of the toxicants or the treatment. This will all help us advance Gulf War treatment development, especially because we include a lengthy interval between our model insult and treatment and evaluate outcomes in our study in the chronic phase.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210194
Entities
People
- Bruce A Citron
Organizations
- United States Army
- Veterans Biomedical Research Institute