Gulf War Illness is a chronic disorder brought on by exposure to sand storms, prophylaxis against chemical warfare, and chronic unpredictable stress. This illness is characterized by neuropsychological and cognitive problems affecting the central nervous system as well as specific organs.
Animal studies of this illness have shown neuroinflammation in several regions of the brain. Treatments used to reduce the neuroinflammation have led to improvements of the neurofunctional abnormalities.
Rosiglitazone and pioglitazone are compounds from the thiazolidinedione family that both have demonstrated neuroprotection in animal models. A new study recently completed at the University of Maryland looked at Gulf War Illness in a rat model and the impact of treatment with rosiglitazone.
Simulation
In order to simulate a Gulf War type of exposure, the rats were subjected to a variety of intense daily stressors for 33 days. Stressors included subjection to restraint, cold, wet, hunger, thirst, and various other types of unpredictably timed environmental stresses. During the 33 days the experimental treatment groups were also administered an oral solution of rosiglitazone each day.
Live Testing
Beginning on day 35, a battery of neurofunctional evaluations was begun. Evaluations included open-field exploration, maze exploration, new object recognition, sucrose preferences, tail suspension response, coat hygiene, splash testing, and forced swimming. These test methods were used as a gauge for cognition, anxiety-like behavior, and depression-like behavior.
Neurofunctional evaluation of the groups showed the development of significant abnormalities in rats exposed to the stressors compared to rats not subjected to such stress. The results of rats exposed to daily stressors and treatment with rosiglitazone were less conclusive. Rosiglitazone treatment seemed to improve measures related to cognition and anxiety, while not having much impact on weight gain or depression.
Tissue Testing
Following the neurofunctional evaluations, the rats were sacrificed so that the brain tissues could be analyzed. Examination of astrocytes, translocator protein, and microglia showed results consistent with a reduced inflammatory response in the samples from the rosiglitazone-treated group.
This modelling of Gulf War Illness successfully induced critical neurofunctional abnormalities, while the concurrent treatment with rosiglitazone reduced the development or abnormalities and neuroinflammation. The model will be useful for further study of the impact and potential treatments for Gulf War Illness.
Learn more about Gulf War Illness on Wikipedia
Thiazolidinediones Available:
Keledjian K, Tsymbalyuk O, Semick S, et al. The peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone, ameliorates neurofunctional and neuroinflammatory abnormalities in a rat model of Gulf War Illness. PLoS One. 2020 Nov 13;15(11):e0242427. PMID: 33186383