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However, practical and convenient preventive strategies for HACE are lacking. Remote ischemic preconditioning (RIPC) has demonstrated preventive effects on ischemia\u2010 or hypoxia\u2010induced cardiovascular and cerebrovascular diseases. This study aimed to investigate the potential molecular mechanism of HACE and the application of RIPC in preventing HACE onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A hypobaric hypoxia chamber was used to simulate a high\u2010altitude environment of 7000 meters. Metabolomics and metabolic flux analysis were employed to assay metabolite levels. Transcriptomics and quantitative real\u2010time PCR (q\u2010PCR) were used to investigate gene expression levels. Immunofluorescence staining was performed on neurons to label cellular proteins. The fluorescent probes Mito\u2010Dendra2, iATPSnFR1.0, and CMTMRos were used to observe mitochondria, ATP, and membrane potential in cultured neurons, respectively. TUNEL staining was performed to detect and quantify apoptotic cell death. Hematoxylin and eosin (H&amp;E) staining was utilized to analyze pathological changes, such as tissue swelling in cerebral cortex samples. The Rotarod test was performed to assess motor coordination and balance in rats. Oxygen\u2013glucose deprivation (OGD) of cultured cells was employed as an in\u00a0vitro model to simulate the hypoxia and hypoglycemia induced by RIPC in animal experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We revealed a causative perturbation of glucose metabolism in the brain preceding cerebral edema. Ischemic preconditioning treatment significantly reprograms glucose metabolism, ameliorating cell apoptosis and hypoxia\u2010induced energy deprivation. Notably, ischemic preconditioning improves mitochondrial membrane potential and ATP production through enhanced glucose\u2010coupled mitochondrial metabolism. In\u00a0vivo studies confirm that RIPC alleviates cerebral edema, reduces cell apoptosis induced by high\u2010altitude hypoxia, and improves motor dysfunction resulting from cerebral edema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study elucidates the metabolic basis of HACE pathogenesis. This study provides a new strategy for preventing HACE that RIPC reduces brain edema through reprogramming metabolism, highlighting the potential of targeting metabolic reprogramming for neuroprotective interventions in neurological diseases caused by ischemia or hypoxia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70026","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T01:11:27Z","timestamp":1725325887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Remote ischemic preconditioning prevents high\u2010altitude cerebral edema by enhancing glucose metabolic reprogramming"],"prefix":"10.1111","volume":"30","author":[{"given":"Rongrong","family":"Han","sequence":"first","affiliation":[{"name":"Beijing Advanced Innovation Center for Big Data\u2010Based Precision Medicine Beihang University  Beijing 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