{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:29:21Z","timestamp":1790274561385,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Neurofilament light Chain (NfL) is a promising brain injury biomarker which may assist diagnosis and prognostication in hypoxic-ischemic encephalopathy (HIE). The aim of this study was to investigate serum NfL levels after hypoxia-ischemia (HI) in a newborn piglet model. Second, to characterize the influence of sex, weight, and treatment with remote ischemic postconditioning (RIPC) on NfL and the correlation between NfL, brain imaging and histologic brain injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used serum from 48 newborn piglets of both sexes subjected to 45\u2005min of global HI, and 4 sham piglets. Blood was collected pre-HI, 2\u2005h post-HI and 72\u2005h post-HI. NfL was measured by single-molecule array (Simoa\u2122). We analysed the temporal profile of NfL after HI, and correlations between NfL, magnetic resonance spectroscopy brain Lac\/NAA ratios and histologic brain injury 72\u2005h after HI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Median (IQR) NfL levels were: pre-HI: 66\u2005pg\/ml (45\u201387), 2\u2005h post-HI: 105\u2005pg\/ml (77\u2013140), and 72\u2005h post-HI: 380\u2005pg\/ml (202\u2013552). The increase in NfL after HI was statistically significant (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001, mixed-effects ANOVA). Median NfL levels in sham animals were 41.4\u2005pg\/ml at baseline and 92.4\u2005pg\/ml at 72\u2005h (<jats:italic>p<\/jats:italic>\u2009=\u20090.11, paired t-test). Neither sex, nor treatment with RIPC influenced NfL levels. Weight had a small, not biologically important, influence. NfL levels at 72\u2005h were moderately correlated with histologic brain injury and brain Lac\/NAA ratios. NfL 72\u2005h post-HI\u2009&amp;gt;\u2009330\u2005pg\/ml had a sensitivity of 89% (95% CI, 57%\u201399%) and a specificity of 52% (95% CI, 34%\u201369%) for predicting basal ganglia Lac\/NAA ratio in the highest quartile. NfL 72\u2005h post-HI\u2009&amp;gt;\u2009445\u2005pg\/ml had a sensitivity of 90% (95% CI, 60%\u201399%) and a specificity of 74% (95% CI, 58%\u201386%) for predicting cortical brain histopathology injury in the highest quartile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NfL increased after HI, with the largest values at 72\u2005h post-HI. Early NfL was sensitive but not very specific, whereas NfL at 72\u2005h was both highly sensitive and specific for exposure to moderate-severe HI in this model of HI-induced brain injury. This was supported by a moderate correlation of NfL at 72\u2005h with brain Lac\/NAA ratio and histopathology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.1068380","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T16:09:12Z","timestamp":1673366952000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Neurofilament Light Chain serum levels after Hypoxia-Ischemia in a newborn piglet model"],"prefix":"10.3389","volume":"10","author":[{"given":"Kasper Jacobsen","family":"Kyng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Wellmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Lehnerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e6rke 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