Differential Responses of Primary Astrocytes under Hyperthermic Temperatures

Astrocyte is the most abundant cells in brain and plays critical roles in brain homeostasis and functions. Although hyperthermia (or fever) is a common symptom in patients, its influence on astrocyte viability, morphology, and functions remains elusive. Here we developed an in vitro astrocyte culture system capable of precisely controlling culture temperature to study astrocyte responses under clinically-relevant hyperthermic temperatures (38 ∼ 41 °C). We found that hyperthermia in this temperature range does not alter cell morphology, but significantly affects cell viability, activation and functions. Specifically, high-hyperthermia (40 °C and 41 °C) causes irreversible and permanent damages to astrocytes and compromises their normal viability and functionalities repairing damaged neural tissue, recycling neurotransmitters, and promoting brain development, while mild-hyperthermia (38 °C and 39 °C) induces astrocyte activation and cytokine secretion without significant decreases in cell viability. This study sheds new insights into our understanding of various fever-associated symptoms, enabling the future development of astrocyte-targeted therapy to treat brain diseases via hyperthermia.