With the advancement of the Belt and Road Initiative and increasing activity in high-altitude regions, the incidence of high-altitude-related diseases has steadily increased. Notably, the prevention and treatment of high-altitude brain injuries remain particularly challenging, making them a key focus of current medical research. The low-pressure and low-oxygen environments at high altitudes significantly increase the risk of hypoxic brain injury. Consequently, understanding the mechanisms that drive these injuries and developing targeted treatments are crucial for maintaining the health of individuals who rapidly ascend to high altitudes. This review examines the mechanisms underlying high-altitude brain injury, outlines the development and evaluation of commonly used animal models for altitude stress, and explores potential therapeutic approaches to support effective prevention and treatment strategies for these conditions.