Pathophysiological basis and promise of experimental therapies for Gulf War Illness, a chronic neuropsychiatric syndrome in veterans

This article describes the pathophysiology and potential treatments for Gulf War Illness (GWI), which is a chronic neuropsychiatric illness linked to a combination of chemical exposures experienced by service personnel during the first Gulf War in 1991. However, there is currently no effective treatment for veterans with GWI. The article focuses on the current status and efficacy of existing therapeutic interventions in preclinical models of GWI, as well as potential perspectives of promising therapies. GWI stems from changes in brain and peripheral systems in veterans, leading to neurocognitive deficits, as well as physiological and psychological effects resulting from multifaceted changes such as neuroinflammation, oxidative stress, and neuronal damage. Aging not only renders veterans more susceptible to GWI symptoms, but also attenuates their immune capabilities and response to therapies. A variety of experimental models are being used to investigate the pathophysiology and develop therapies that have the ability to alleviate devastating symptoms. Over two dozen therapeutic interventions targeting neuroinflammation, mitochondrial dysfunction, neuronal injury, and neurogenesis are being tested, including agents such as curcumin, curcumin nanoparticles, monosodium luminol, melatonin, resveratrol, fluoxetine, rolipram, oleoylethanolamide, ketamine, levetiracetam, nicotinamide riboside, minocycline, pyridazine derivatives, and neurosteroids. Preclinical outcomes show that some agents have promise, including curcumin, resveratrol, and ketamine, which are being tested in clinical trials in GWI veterans. Neuroprotectants and other compounds such as monosodium luminol, melatonin, levetiracetam, oleoylethanolamide, and nicotinamide riboside appear promising for future clinical trials. Neurosteroids have been shown to have neuroprotective and disease-modifying properties, which makes them a promising medicine for GWI. Therefore, accelerated clinical studies are urgently needed to evaluate and launch an effective therapy for veterans displaying GWI.