Optimizing a mouse model of exertional heat stroke to simulate multiorgan and brain injuries

Abstract: BACKGROUND: Exertional heat stroke (EHS) is a clinical entity characterized by abnormalities of the central nervous system (CNS) and is associated with multiple organ injury, some of which may be irreversible. It is valuable to establish an optimized model of EHS that is able to induce and assess damage to the CNS and multiple organs. METHODS: We induced EHS by using an environmental chamber with adjustable temperature and humidity and a mice forced running wheel. The endpoint for the EHS was defined as either exhaustion or a core temperature of 42.5°C being reached. Injury to the liver, kidney, and CNS of mice in the EHS group was revealed through pathological studies using hematoxylin and eosin staining of harvested organs at different time points and detection of biomarkers. The depressive-like behavior of EHS mice was assessed through open field tests, forced swimming tests, and tail suspension tests. RESULTS: The favorable environmental conditions for induction of EHS based on this presented model are 38°C, 70% RH. The EHS mice developed thermoregulatory dysfunction and experienced a significantly higher weight loss ratio compared to the SHE (sham heat exercise) group. The liver, kidney, and brain tissues of EHS mice were significantly damaged, and the pathological damage scores for each organ were significantly higher than those of the SHE group. In the open field test (OFT), compared to the SHE group, there was a significant reduction in the number and time of EHS mice entering the center of the open field. Additionally, there was a significant increase in immobile time during forced swimming test (FST) and tail suspension test (TST). CONCLUSION: This study presents an improved animal model that has the potential to assess for neurological and multiple organ injury caused by EHS and simultaneously, while accurately reflecting the clinical characteristics observed in EHS patients.