Hypothalamic gene expression profiles during heat stroke recovery in a conscious mouse model

Heat stroke (HS) induces a dynamic thermoregulatory response that consists of a progression from hyperthermia (Tc,Max=42.7°C), to hypothermia (29.3±0.4°C) followed by a delayed fever (37.8±0.3°C) that develops within ~24h. This response is accompanied by behavioral and metabolic changes that suggest these are tightly regulated responses. The physiological mechanisms underlying these responses are unknown. We hypothesized that distinct hypothalamic gene expression profiles of heat shock protein (HSP)‐72, cytokines (IL‐1β, IL‐6, TNFα, MIP‐1β), cyclooxygenase (COX‐2) and microglia activation markers (MHCII, CD200) would associate with each stage of the response in a conscious mouse model. HSP‐72 showed a 7.7‐ and 15.8‐fold increase from Tc,Max to hypothermia, with return to baseline by 24h (P<0.001). MIP‐1β showed a 9.5‐fold increase at hypothermia only (P<0.001). Peak expression of IL‐6 (4.4‐fold) and COX‐2 (12.8‐fold) occurred at hypothermia, but these cytokines remained elevated above controls through 24h. IL‐1β (3.6‐fold) and TNFα (3.6‐fold) showed peak expression during fever (P<0.001). No significant changes in microglia activation markers were observed. These data suggest that distinct changes in hypothalamic cytokines and COX products may regulate the different thermoregulatory responses to HS. Author views not official US Army or DoD policy.