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dc.contributor.authorLindblad, Carolineen
dc.contributor.authorNelson, David Wen
dc.contributor.authorZeiler, Frederick Aen
dc.contributor.authorErcole, Arien
dc.contributor.authorGhatan, Per Hamiden
dc.contributor.authorvon Horn, Henriken
dc.contributor.authorRisling, Mårtenen
dc.contributor.authorSvensson, Mikaelen
dc.contributor.authorAgoston, Denes Ven
dc.contributor.authorBellander, Bo-Michaelen
dc.contributor.authorThelin, Ericen
dc.date.accessioned2020-02-01T00:32:24Z
dc.date.available2020-02-01T00:32:24Z
dc.date.issued2020-06en
dc.identifier.issn0897-7151
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301604
dc.description.abstractBrain protein biomarker clearance to blood in traumatic brain injury (TBI) is not fully understood. The aim of this study was to analyze the effect a disrupted blood-brain barrier (BBB) had on biomarker clearance. Seventeen severe TBI patients admitted to Karolinska University Hospital were prospectively included. Cerebrospinal fluid (CSF) and blood concentrations of S100B and neuron-specific enolase (NSE) were analyzed every 6-12 hours for approximately one week. A). dependent changes in the CSF and blood levels of the two biomarkers were similar but the correlation between the biomarkers and QA was lower for NSE (=0.444) than S100B (=0.668). Since data was longitudinal, we also conducted cross correlation analyses, which indicated a directional flow and lag-time of biomarkers from CSF to blood. For S100B, this lag-time could be ascribed to BBB integrity, whereas for NSE it could not. Upon inferential modelling, using generalized least square estimation (S100B) or linear mixed models (NSE), QA (p=0.045), time from trauma (p<0.001), time from trauma2 (p=0.023) and CSF biomarker levels (p=0.008) were independent predictors of S100B in blood. In contrast, for NSE, only time from trauma was significant (p<0.001). These findings are novel and important, but must be carefully interpreted because of different characteristics between the two proteins. Nonetheless, we present the first data that indicates that S100B and NSE are cleared differently from the central nervous system, and that both the disrupted BBB and additional alternative pathways, such as the recently described glymphatic system, may play a role. This is of importance both for clinicians aiming to utilize these biomarkers and for the pathophysiological understanding of brain protein clearance, but warrants further examination.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherMary Ann Liebert
dc.rightsAll rights reserved
dc.rights.uri
dc.titleInfluence of Blood-Brain Barrier Integrity on Brain Protein Biomarker Clearance in Severe Traumatic Brain Injury: A Longitudinal Prospective Study.en
dc.typeArticle
prism.endingPage1391
prism.issueIdentifier12en
prism.publicationDate2020en
prism.publicationNameJournal of neurotraumaen
prism.startingPage1381
prism.volume37en
dc.identifier.doi10.17863/CAM.48673
dcterms.dateAccepted2020-01-28en
rioxxterms.versionofrecord10.1089/neu.2019.6741en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-06en
dc.contributor.orcidZeiler, Frederick A [0000-0003-1737-0510]
dc.contributor.orcidErcole, Ari [0000-0001-8350-8093]
dc.contributor.orcidThelin, Eric [0000-0002-2338-4364]
dc.identifier.eissn1557-9042
rioxxterms.typeJournal Article/Reviewen
cam.orpheus.successTue Mar 31 10:37:32 BST 2020 - Embargo updated*
rioxxterms.freetoread.startdate2021-03-06


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