Rosuvastatin ameliorates high-altitude cerebral edema by promoting blood-brain barrier integrity via the regulation of energy metabolism.

High-altitude cerebral edema (HACE) is a severe and potentially fatal neurological condition resulting from acute exposure to hypobaric hypoxia. This condition is characterized by the disruptions of endothelial tight junctions, triggering blood-brain barrier (BBB) compromise and subsequent vasogenic edema. However, the effective protective strategies against HACE remain limited. The present research aimed to elucidate the protective effects of Rosuvastatin on HACE in rats and the underlying mechanisms. Rats were exposed to hypobaric hypoxia at an altitude equivalent to 6000 m for 24 h. Subsequently, analyses of brain structure, BBB integrity, and mitochondrial energy metabolism were performed to confirm the protective efficacy of Rosuvastatin against BBB disruption in HACE. The findings revealed that Rosuvastatin significantly maintained BBB integrity by promoting tight junctions in vascular endothelial cells of rats exposed to hypobaric hypoxia. Simultaneously, Rosuvastatin effectively mitigated hypobaric hypoxia-induced oxidative stress by reducing the formation of reactive oxygen species and malondialdehyde, while enhancing the activity of glutathione peroxidase and superoxide dismutase in brain tissue. Importantly, Rosuvastatin markedly attenuated mitochondrial function by enhancing oxidative phosphorylation. Collectively, our findings first demonstrated that Rosuvastatin mitigates HACE progression by modulating oxidative stress and mitochondrial energy metabolism.