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However, the specific mechanisms underlying its pathogenesis and progression remain incompletely understood. In this review, we demonstrate that immigrant populations subjected to chronic high\u2010altitude exposure are at increased risk of ICH relative to indigenous populations (Tibetans, Andeans), primarily due to the lack of adaptive genetic variations such as endothelial PAS domain protein 1 and small ubiquitin\u2010like modifier\u2010specific peptidase 1. Additionally, high\u2010altitude polycythemia, high\u2010altitude hypertension, and hyperuricemia have been identified as critical risk factors for high\u2010altitude ICH. Further mechanistic exploration reveals that chronic high\u2010altitude exposure\u2010induced brain injury is structurally underpinned by vascular\u2010immune\u2010neuronal network dysfunction, which entails the interactive crosstalk of \u201cvascular injury\u2010immune infiltration\u2010neurodegeneration\u201d and thereby creates a unique pathological niche for high\u2010altitude ICH. At the molecular level, the core driving mechanism is the reciprocal activation of the hypoxia\u2010inducible factor pathway, oxidative stress, and neuroinflammation. This review represents a comprehensive synthesis of chronic high\u2010altitude exposure\u2010related brain injury and the subsequent exacerbation of ICH, providing a valuable reference for future research on high\u2010altitude encephalopathy.<\/jats:p>","DOI":"10.1002\/nep3.70059","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:01:01Z","timestamp":1791180061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic high\u2010altitude exposure and intracerebral hemorrhage: A novel perspective from the vascular\u2010immune\u2010neuronal network"],"prefix":"10.1002","author":[{"given":"Rongsu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Department of Neurosurgery General Hospital of Xizang Military Command Lhasa Xizang China"},{"name":"Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The 956th Hospital of the Chinese People's Liberation Army Linzhi Xizang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chongqing General Hospital Chongqing University School of Medicine Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjian","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The 945th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force Ya'an Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9905-9138","authenticated-orcid":false,"given":"Yujie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 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