Table 1 Chemical agents and surrogates commonly employed to model Gulf War era exposures
From: Chemical exposures and suspected impact on Gulf War Veterans
Author | Model | Agent of exposure | Type of chemical | Duration of exposure/concentration | Target system/organ studied | Symptomatic model targets | Results |
|---|---|---|---|---|---|---|---|
Koo et al. [11] | Rat | CORT DFP | CORT – simulate organic stress reaction DFP – OP; sarin nerve agent surrogate | CORT in drinking water (200 mg/L in 0.6% EtOH) for 4 d, followed by a single injection of DFP (1.5 mg/kg, i.p.) | Evaluation of cerebral cortex | Neuroinflammation, cognitive impairment, sickness behavior | CORT exacerbates the neuroinflammatory response of DFP |
Miller et al. [12] | Mouse | CPO DFP PHY CORT | CPO, PHY, DFP as surrogates for AChEIs | CPO (8Â mg/kg), DFP (4Â mg/kg), or PHY (0.5Â mg/kg) was administered in the morning and returned to their home cage. CORT was given in the drinking water (400Â mg/L in 1.2% EtOH) for 4 d prior to AChEI or vehicle exposure | Whole brain tissue | Neuroinflammation and general GWI symptomology | CORT blunts the impact of irreversible AChEI on AChE in the brain while exacerbating DFP and CPO neuroinflammatory response |
O’Callaghan et al. [13] | Mouse | CORT DFP DEET | DEET is a common insecticide that was possibly overused in the GW | Mice were dosed once per day for 14 d with PB [2 mg/(kg·d), s.c.] and DEET [30 mg/(kg·d), s.c]. On days 8 – 15, mice received CORT in the drinking water (200 mg/L in 1.2% ethanol, EtOH). Finally, on day 15, mice were treated with a single injection of either DFP (4 mg/kg, i.p.) or saline | Frontal cortex Hippocampus Striatum Hypothalamus Olfactory bulbs Cerebellum | Neuroinflammation and sickness behavior | Mice exposed to DFP and CORT had a 300-fold exacerbated neuroinflammatory response compared to DFP alone |
Murray et al. [14] | Mouse | PB CPF DEET | GW-related exposures to model prophylaxis, insecticides, and insect repellent | Mice were exposed daily for 2Â weeks followed by RNA sequencing analysis of hippocampal tissue | Hippocampus | Neuronal health and cognition | Exposures resulted in enhanced gene expression profiles related to inflammation while decreasing expression of genes positively regulating neuronal health |
Michalovicz et al. [15] | Mouse | Propranolol | Beta blocker | 20 mg/kg in saline with CORT (200 mg/L in drinking water) or after exposure to CORT | Whole brain tissue | Neuroinflammation | Propranolol reduced mRNA expression of inflammatory cytokines such as TNF-α, CCL2, IL-1β in both the hippocampus and the cortex in the GWI model compared to normal healthy mice |
Zakirova et al. [16] | Mouse | PB Permethrin | Nerve agent prophylaxis and pesticide | Daily injections for 10 d followed by cognitive and immunohistochemical staining at day 18 and at 5Â months | Hippocampus Cerebral cortex | Cognitive impairment and astrogliosis | Exposure agents had little to no effect in the short term (18 d). At 5Â months, treated animals exhibited cognitive impairments and astrogliosis |
Patterson et al. [17] | Mouse | DFP CORT | Model for OP exposure and stress | CORT (200Â mg/L) in drinking water for 7 d followed by DFP (1Â mg/kg) on day 8 | Intestinal tissue | Gastrointestinal dysfunction and neuroinflammation | Exposure to DFP reduces the expression of the intestinal tight junctions occludin |
Jang et al. [18] | Mouse | CPF | Metabolite of CPO | Chronic treatment: mice were injected with 3Â mg/kg of CPF for 14 d. Single dose treatment: mice were injected with 3Â mg/kg of CPF | Whole brain Plasma | Skin toxicity and inflammation | CPF increased the levels of ROS in a human skin keratinocyte cell line (HaCaT) |