{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:14:58Z","timestamp":1791220498019,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"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>Objective<\/jats:title><jats:p>Hypoxia-inducible factor 1alpha (HIF-1\u03b1) functions as a crucial transcriptional mediator in hypoxic and ischemic brain response. We endeavored to assess the prognostic significance of serum HIF-1\u03b1 in human aneurysmal subarachnoid hemorrhage (aSAH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective, longitudinal, multicenter, and observational study of 257 patients with aSAH and 100 healthy controls, serum HIF-1\u03b1 levels were quantified. Univariate analyses, followed by multivariate analyses, were performed to discern the relationship between serum HIF-1\u03b1 levels and severity and delayed cerebral ischemia (DCI) plus poststroke 6-month poor outcome [extended Glasgow outcome scale (GOSE) scores of 1\u20134]. Predictive efficiency was determined under the receiver operating characteristic (ROC) curve.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were significantly increased serum HIF-l\u03b1 levels after aSAH, in comparison to controls (median, 288.0 vs. 102.6 pg\/ml; <jats:italic>P<\/jats:italic> &amp;lt; 0.001). Serum HIF-l\u03b1 levels were independently correlated with Hunt\u2013Hess scores [\u03b2, 78.376; 95% confidence interval (CI): 56.446\u2013100.305; <jats:italic>P<\/jats:italic> = 0.001] and modified Fisher scores (\u03b2, 52.037; 95% CI: 23.461\u201380.614; <jats:italic>P<\/jats:italic> = 0.002). Serum HIF-l\u03b1 levels displayed significant efficiency for discriminating DCI risk [area under ROC curve (AUC), 0.751; 95% CI: 0.687\u20130.815; <jats:italic>P<\/jats:italic> &amp;lt; 0.001] and poor outcome (AUC, 0.791; 95% CI: 0.736\u20130.846; <jats:italic>P<\/jats:italic> &amp;lt; 0.001). Using the Youden method, serum HIF-1\u03b1 levels &amp;gt;229.3 pg\/ml predicted the development of DCI with 92.3% sensitivity and 48.4% specificity and serum HIF-1\u03b1 levels &amp;gt;384.0 pg\/ml differentiated the risk of a poor prognosis with 71.4% sensitivity and 81.1% specificity. Serum HIF-1\u03b1 levels &amp;gt;229.3 pg\/ml were independently predictive of DCI [odds ratio (OR), 3.061; 95% CI: 1.045\u20138.965; <jats:italic>P<\/jats:italic> = 0.041] and serum HIF-1\u03b1 levels &amp;gt;384.0 pg\/ml were independently associated with a poor outcome (OR, 2.907; 95% CI: 1.403\u20136.024; <jats:italic>P<\/jats:italic> = 0.004). The DCI predictive ability of their combination was significantly superior to those of Hunt\u2013Hess scores (AUC, 0.800; 95% CI: 0.745\u20130.855; <jats:italic>P<\/jats:italic> = 0.039) and modified Fisher scores (AUC, 0.784; 95% CI: 0.726\u20130.843; <jats:italic>P<\/jats:italic> = 0.004). The prognostic predictive ability of their combination substantially exceeded those of Hunt\u2013Hess scores (AUC, 0.839; 95% CI: 0.791\u20130.886; <jats:italic>P<\/jats:italic> &amp;lt; 0.001) and modified Fisher scores (AUC, 0.844; 95% CI: 0.799\u20130.890; <jats:italic>P<\/jats:italic> &amp;lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Elevated serum HIF-l\u03b1 levels after aSAH, in independent correlation with stroke severity, were independently associated with DCI and 6-month poor outcome, substantializing serum HIF-l\u03b1 as a potential prognostic biomarker of aSAH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.1072351","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T05:11:55Z","timestamp":1670476315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Potential role of serum hypoxia-inducible factor 1alpha as a biomarker of 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