Cerebellar HSP70 Remains Elevated During Heat Stroke Recovery despite Return to Baseline Core Temperature

Abstract

Heat Stroke (HS) remains a significant health threat for civilians and U.S. Armed Forces. Unknown is whether return to normal core temperature (Tc; ±0.1°C, radiotelemetry) within 2 days of HS is an accurate indicator of full recovery. Cerebellar damage is implicated in HS sequelae, but inflammatory responses in this brain region during prolonged recovery have not been investigated. We hypothesized that the cerebellum would show a differential time course of HS recovery compared to Tc during 7 days of HS recovery. C57BL/6J mice (N=3‐7/group) were heated to Tc of 42.4ºC and the cerebellum was extracted at 4 time points (3 hours, 1, 2, and 7 days) of recovery. Twelve common HS biomarkers were examined using rtPCR, ELISA, and Western Blot. There were no changes in any genes at 7 days, indicating normalization of expression. HSP70 protein peaked at day 1 and remained elevated through 7 days. At 3h, five cytokine genes (IL6, HSP70, TNFα, HSF‐1, IL‐1β) and three chemokine genes (Ccl2, Ccl3, Ccl4) were elevated, while one chemokine (Ccl5) was down‐regulated. At 1 day, only Ccl2 was still significantly elevated, yet returned to baseline levels by 2 days. Elevated HSP70 protein at 7 days following HS suggests persistent protein denaturation, which could indicate incomplete recovery even though other inflammatory markers and Tc have returned to normal. These data suggest that a return to normal Tc should not be the only indicator for HS recovery and persistent inflammatory changes may be occurring in the brain through 7 days. Author views not official US Army or DoD policy.