Long-term changes in neuroimaging markers, cognitive function and psychiatric symptoms in an experimental model of...

Gulf War Illness (GWI) is a multi-symptom disease with debilitating cognitive and emotional impairments in veterans. GWI, like epilepsy, is caused by chemical neurotoxicity and manifests from disturbances in neuronal excitability. However, the mechanisms underlying such devastating neurological and psychiatric symptoms remain unclear. Here we investigated the long-term changes in neural behavior and brain structural abnormalities in a rat model of GWI. GWI is linked to exposure to GWI-related organophosphate chemicals (pyridostigmine bromide or PB and insecticide DEET, permethrin) during the stressful Gulf war.

To mimic GWI, we generated an experimental GWI prototype in rats by daily exposure to GWI-related chemicals with restraint stress (GWIR-CS) for 4 weeks. Changes in MRI scan and cognitive function were assessed at 5- and 10- months post-exposure.

In MRI scans, rats displayed significant increases in lateral ventricle T2 relaxation times at both 5- and 10-months after GWIR-CS, indicating alterations in the cerebrospinal fluid (CSF) density. Furthermore, at 10 months, there were significant decreases in the volumes of the hippocampus and thalamus and an increase in the lateral ventricle volume. At both time points, they exhibited impairments in multiple neurobehavioral tests, confirming substantial deficits in memory and mood function. GWI-CS rats also displayed aggressive behavior and a marked decrease in social interaction and forced swimming, indicating depression.

These results confirm that chronic GWIR-CS exposure led to cognitive and psychiatric symptoms with concurrent neuroimaging abnormalities in CSF, with morphological neural lesions, demonstrating the role of divergent etiological mechanisms in GWI and its comorbidities.