{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:20:17Z","timestamp":1783099217733,"version":"3.54.6"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Erythropoietin (EPO) plays a crucial role in the early adaption to high altitude and is possibly involved in neuroprotection. Neurofilament light chain (NfL) is an established marker of neuroaxonal damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether EPO dynamics in simulated high altitude are linked to neuroaxonal damage as measured by NfL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty-three healthy subjects were exposed to simulated altitude of 4,500\u202fm for 12\u202fh in a normobaric hypoxic chamber at the University of Innsbruck. Clinical data (heart rate, arterial oxygen saturation) were assessed before and 3\u202fh after high altitude exposure; plasma samples were drawn before (measurement (M) 1) and after 12\u202fh (M2). The levels of EPO and hypoxia-inducible factor (HIF)-1\u03b1 were quantified using commercially available ELISA kits. NfL concentrations were measured using the Simoa SR-X Analyzer, and NfL Z scores calculated using age- and body mass index (BMI)-adjusted reference values.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EPO significantly increased after 12\u202fh (M2: 10.12 [7.86\u201314.06] mU\/mL vs. M1: 4.17 [2.99\u20135.67] mU\/mL, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), while HIF-1\u03b1 did not significantly change (<jats:italic>p<\/jats:italic>\u202f=\u202f0.409). Subjects with high EPO levels at M2 showed significantly lower NfL concentrations (5.85 [4.15\u20136.85] pg\/mL vs. 6.73 [4.70\u20138.64] pg\/mL, <jats:italic>p<\/jats:italic>\u202f=\u202f0.030) as well as lower NfL Z scores (0.64 [\u22120.88\u20131.17] vs. 0.95 [0.25\u20131.48], <jats:italic>p<\/jats:italic>\u202f=\u202f0.040) than those with low EPO levels. The extent of heart rate increase showed a positive correlation with EPO levels at M2 (r<jats:sub>s<\/jats:sub>\u202f=\u202f0.322, <jats:italic>p<\/jats:italic>\u202f=\u202f0.011).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Higher EPO concentrations were associated with lower NfL levels. This might further substantiate the hypothesis of a neuroprotective role of EPO.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1608763","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:26:44Z","timestamp":1753698404000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["High erythropoietin levels are associated with low neurofilament light levels in simulated high altitude: a further hint for neuroprotection by 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