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In this study, adult male Sprague-Dawley rats were randomly assigned to five groups: Control, HH, HH with low-dose dexmedetomidine (Dex), HH with high-dose Dex, and Control with Dex. Rats were exposed to a simulated 6000-meter altitude for 7 days. Behavioral tests, enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative PCR (RT-qPCR), and Western blotting were used to assess hormone levels, gene\/protein expression, and inflammatory markers. HH exposure elevated hypothalamic serotonin (5-hydroxytryptamine, 5-HT) and reduced melatonin levels. The sleep rhythm-related gene Timeless was downregulated, while Homer1 was upregulated at both mRNA and protein levels. Knockdown of Timeless or overexpression of Homer1 resulted in a significant increase in hypothalamic 5-HT levels and a marked decrease in melatonin levels. HH induced enhanced anxiety-like behaviors and reduced spontaneous activity, accompanied by elevated levels of L-1\u03b2, IL-6, and TNF-\u03b1 in both serum and hypothalamus. Inhibition of the TLR4-MyD88-NF\u03baB pathway significantly alleviated both hormonal disturbances and anxiety-like behaviors in HH rats.Dex treatment, especially at high doses, suppressed inflammatory responses, normalized hormone levels, restored sleep gene expression, and improved behavioral outcomes. These results indicate that dex mitigates HH-induced sleep and inflammatory disturbances, highlighting its therapeutic potential for high-altitude neurological dysfunction.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13105-025-01127-1","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:14:53Z","timestamp":1762928093000},"page":"1125-1141","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dexmedetomidine regulates sleep rhythm and alleviates neuroinflammation in rats under high-altitude hypoxia"],"prefix":"10.1007","volume":"81","author":[{"given":"Shanshan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhe","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhe","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"1127_CR1","doi-asserted-by":"publisher","first-page":"ii40","DOI":"10.1093\/eurjpc\/zwad185","volume":"30","author":"C Vignati","year":"2023","unstructured":"Vignati C, Contini M, Salvioni E et al (2023) Exercise in hypoxia: a model from laboratory to on-field studies. 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