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Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["U54NS100064"],"award-info":[{"award-number":["U54NS100064"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Plasma neurofilament light chain (NF-L) levels were assessed as a diagnostic biomarker for traumatic brain injury (TBI) and as a prognostic biomarker for somatomotor recovery, cognitive decline, and epileptogenesis. Rats with severe TBI induced by lateral fluid-percussion injury (n = 26, 13 with and 13 without epilepsy) or sham-operation (n = 8) were studied. During a 6-month follow-up, rats underwent magnetic resonance imaging (MRI) (day (D) 2, D7, and D21), composite neuroscore (D2, D6, and D14), Morris-water maze (D35\u2013D39), and a 1-month-long video-electroencephalogram to detect unprovoked seizures during the 6th month. Plasma NF-L levels were assessed using a single-molecule assay at baseline (i.e., na\u00efve animals) and on D2, D9, and D178 after TBI or a sham operation. Plasma NF-L levels were 483-fold higher on D2 (5072.0 \u00b1 2007.0 pg\/mL), 89-fold higher on D9 (930.3 \u00b1 306.4 pg\/mL), and 3-fold higher on D176 32.2 \u00b1 8.9 pg\/mL after TBI compared with baseline (10.5 \u00b1 2.6 pg\/mL; all p &lt; 0.001). Plasma NF-L levels distinguished TBI rats from na\u00efve animals at all time-points examined (area under the curve [AUC] 1.0, p &lt; 0.001), and from sham-operated controls on D2 (AUC 1.0, p &lt; 0.001). Plasma NF-L increases on D2 were associated with somatomotor impairment severity (\u03c1 = \u22120.480, p &lt; 0.05) and the cortical lesion extent in MRI (\u03c1 = 0.401, p &lt; 0.05). Plasma NF-L increases on D2 or D9 were associated with the cortical lesion extent in histologic sections at 6 months post-injury (\u03c1 = 0.437 for D2; \u03c1 = 0.393 for D9, p &lt; 0.05). Plasma NF-L levels, however, did not predict somatomotor recovery, cognitive decline, or epileptogenesis (p &gt; 0.05). Plasma NF-L levels represent a promising noninvasive translational diagnostic biomarker for acute TBI and a prognostic biomarker for post-injury somatomotor impairment and long-term structural brain damage.<\/jats:p>","DOI":"10.3390\/ijms232315208","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T01:42:21Z","timestamp":1670204541000},"page":"15208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-5240","authenticated-orcid":false,"given":"Mette","family":"Heiskanen","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"J\u00e4\u00e4skel\u00e4inen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine\/Neurology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9353-6079","authenticated-orcid":false,"given":"Eppu","family":"Manninen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Das Gupta","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9118-8341","authenticated-orcid":false,"given":"Pedro","family":"Andrade","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Ciszek","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Gr\u00f6hn","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna-Kaisa","family":"Herukka","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine\/Neurology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"},{"name":"Department of Neurology, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"Puhakka","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8163-5416","authenticated-orcid":false,"given":"Asla","family":"Pitk\u00e4nen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the Global Incidence of Traumatic Brain Injury","volume":"130","author":"Dewan","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107080","DOI":"10.1016\/j.yebeh.2020.107080","article-title":"Biomarkers for Posttraumatic Epilepsy","volume":"121","author":"Paananen","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_3","first-page":"e17056","article-title":"Systematic Review of Serum Biomarkers in Traumatic Brain Injury","volume":"13","author":"Mozaffari","year":"2021","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Krausz, A.D., Korley, F.K., and Burns, M.A. (2021). 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