Research advances of the molecular mechanisms of brain injury in high-altitude environment
CAO Zixuan
LI Tianjing
LIU Dan
ZHANG Zhuoyuan
LUO Peng
Abstract：The low-pressure,low-oxygen environment of plateaus has been shown to have a significant influence on the occurrence and development of acute and chronic plateau brain injury.Intense exposure can induce acute mountain sickness(AMS)and high-altitude cerebral oedema(HACE),which is manifested by blood-brain barrier(BBB)disruption,mitochondrial dysfunction,and neuroinflammation.Prolonged residence,on the other hand,is closely associated with high-altitude polycythemia(HAPC)and neurodegenerative changes(e.g.,Alzheimer's disease).This review systematically summarises the molecular mechanisms of plateau brain injury:Firstly,the activation of the hypoxia-inducible factor(HIF)pathway exacerbates brain injury by modulating vascular permeability,oxidative stress and inflammatory responses.Secondly,mitochondrial dysfunction leads to energy metabolism disorders and ROS accumulation.Thirdly,microglia M1 polarisation and NLRP3 inflammatory vesicle activation drive neuroinflammation.Finally,chronic hypoxia is associated with Aβ deposition through tau phosphorylation and autophagy loss,tau phosphorylation and autophagy dysregulation promoting neurodegeneration.With regard to intervention strategies,the efficacy of antioxidants(e.g.,Nrf2 activators),HIF pathway modulation(e.g.,roxarestat),and lifestyle interventions(stepwise habilitation)has been demonstrated.In the future,there is a need to combine multi-omics technology and clinical translational research to make a deep analysis of the molecular network of plateau brain injury,so as to provide the basis for precise prevention and treatment.
Keywords：high-altitude brain injuryhypoxia inducible factoroxidative stressneuroinflammation
Publication Date：2025-12-28
Online Publishing Date：2025-12-02(First online date of this platform, not the publication date of the document)
Pages：6( 162-167 )