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Dynamics of extracellular matrix proteins in cerebrospinal fluid and serum and their relation to clinical outcome in human traumatic brain injury

Journal article
Authors Karolina Minta
N. C. Cullen
F. A. Nimer
E. P. Thelin
F. Piehl
Marcus Clarin
Mats Tullberg
Anna Jeppsson
Erik Portelius
Henrik Zetterberg
Kaj Blennow
Ulf Andreasson
Published in Clinical Chemistry and Laboratory Medicine
Volume 57
Issue 10
Pages 1565–1573
ISSN 1434-6621
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 1565–1573
Language en
Links dx.doi.org/10.1515/cclm-2019-0034
Keywords brevican, neurocan, tenascin-C, tenascin-R, traumatic brain injury
Subject categories Psychiatry, Neurochemistry

Abstract

Brevican, neurocan, tenascin-C and tenascin-R are extracellular matrix proteins present in brain that show increased expression in experimental animal models of brain injury. However, little is known about the dynamics of these proteins in human body fluids, such as cerebrospinal fluid (CSF) and serum, after traumatic brain injury (TBI). The aims of this study were to investigate if matrix proteins in CSF and serum are associated with functional outcome following traumatic brain injury, if their concentrations change over time and to compare their levels between brain injured patients to controls. In total, 42 traumatic brain injury patients, nine healthy controls and a contrast group consisting of 38 idiopathic normal pressure hydrocephalus patients were included. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the concentrations of proteins. Increased concentrations of brevican, tenascin-C and tenascin-R in CSF correlated with unfavourable outcome, with stronger outcome prediction ability compared to other biomarkers of brain tissue injury. CSF brevican, tenascin-R and serum neurocan gradually decreased with time (p = 0.04, p = 0.008, p = 0.005, respectively), while serum tenascin-C (p = 0.01) increased. CSF concentrations of brevican, neurocan and tenascin-R (only in time point 3) after TBI were lower than in the idiopathic normal pressure hydrocephalus group (p < 0.0001, p < 0.0001, and p = 0.0008, respectively). In serum, tenascin-C concentration was higher and neurocan lower compared to healthy controls (p = 0.02 and p = 0.0009). These findings indicate that levels of extracellular matrix proteins are associated with clinical outcome following TBI and may act as markers for different pathophysiology than currently used protein biomarkers. © 2019 Walter de Gruyter GmbH, Berlin/Boston.

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