Non-severe burn injury leads to sustained molecular changes in the brain in a murine model

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.