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Preclinical Model of Military Burn Pit Exposure Reveals Altered Inflammatory and Metabolic Pathways in the Rat Lung-Brain Axis

ABSTRACT: Military personnel deployed to combat zones in Iraq and Afghanistan were exposed to toxic emissions from open-air burn pits, raising concerns about long-term health effects. Burn pit exposures are linked to a wide range of pulmonary and extra-pulmonary morbidities. This study aimed to model military burn pit exposure and investigate its impact on lung-brain axis signaling. Rats were exposed to carbon black nanoparticles and naphthalene (CBN) via whole body inhalation chamber for six hours to simulate burn pit exposure. Gene expression and inflammatory protein changes in lung and brain tissue were examined 24 hours post-exposure using next-generation RNA sequencing, Meso Scale Discovery biomarker assays, and western blot. Multiple inflammatory pathway proteins were significantly altered in plasma, lung and brain. Gene Set Enrichment Analysis (GSEA) in lung and brain revealed significant alterations in molecular processes in lung tissue, including increased cell cycle activity, lipid balance disruption, and enhanced inflammatory responses. Conversely, processes such as adipogenesis, oxidative phosphorylation, and epithelial to mesenchymal transition were suppressed. An elastic net penalized regression model identified a set of 104 genes in lung tissue that could indicate CBN exposure in lung. We focus on the nine genes with the greatest contribution to this model. These genes, including Tiam1, Cpsf3, and Tgfrb1, are involved in various cellular processes such as inflammation, cell signaling, and tissue remodeling. We observed significant increases in lung, brain and peripheral inflammation as well as signaling changes in lung and brain that demonstrate disruption of tissue homeostasis. Our findings demonstrate notable gene expression changes that may represent similarities to Veterans suffering from Deployment-Related Respiratory Disease (DRRD). This study provides insights into the molecular mechanisms underlying lung and brain response to burn pit-like exposures and identifies potential biomarkers for further investigation of the lung-brain axis. These results contribute to our understanding of the health impacts of military burn pit exposures and may inform future diagnostic and therapeutic strategies.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE281993 | GEO | 2025/08/20

REPOSITORIES: GEO

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Project description:Background: Paediatric burn patients, including those with non-severe burns, have an increased risk of admission to hospital for mental health conditions for many years after the burn, even in children too young at the time of the burn to remember the incident. This study aimed to investigate the long-term physiological impact of non-severe burn injuries and non-burn trauma (NBT) on the brain in mice to understand whether there is a sustained impact of such injuries on the brain that may be linked to the increased mental health morbidity observed in patients. Methods: Mice were exposed to either a non-severe burn injury, an excision injury of the same size (equivalent non-burn trauma), or a sham procedure. Behavioural tests were conducted at multiple timepoints to measure anxiety and depression-like behaviour. Mice were euthanised three months after the injury, and plasma and brain tissue, including the hippocampus and prefrontal cortex, were isolated and examined using RNA sequencing, mass spectrometry and nuclear magnetic resonance (NMR) to identify transcriptomic and metabolomic changes. Results: A significant change in behaviour was observed with an increase in sucrose consumption three months after injury in the burn group compared to sham. Significant changes in the transcriptome were identified in some brain regions at 3 months after burn trauma compared to the sham group. Differentially expressed genes associated with inflammatory and immune functions were identified in the burn group compared to controls. Significant changes were also observed in the lipid profile and tryptophan catabolites in the brain after burn trauma compared to sham. Conclusion: Sustained changes in the transcriptome and metabolome were identified in a mouse model of non-severe burns, supporting a likely sustained pro-inflammatory environment in the brain after this type of injury. The potential link between these changes and the poor long-term mental health outcomes observed in paediatric burn patients requires further investigation.

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Preclinical Model of Military Burn Pit Exposure Reveals Altered Inflammatory and Metabolic Pathways in the Rat Lung-Brain Axis

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