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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.

Abstract
Background 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. Methods 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. Results 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). Conclusions 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.
AuthorsKarolina Minta, Nicholas C Cullen, Faiez Al Nimer, Eric P Thelin, Fredrik Piehl, Marcus Clarin, Mats Tullberg, Anna Jeppsson, Erik Portelius, Henrik Zetterberg, Kaj Blennow, Ulf Andreasson
JournalClinical chemistry and laboratory medicine (Clin Chem Lab Med) Vol. 57 Issue 10 Pg. 1565-1573 (Sep 25 2019) ISSN: 1437-4331 [Electronic] Germany
PMID30980710 (Publication Type: Journal Article)
Chemical References
  • Biomarkers
  • Extracellular Matrix Proteins
  • Neurocan
  • Tenascin
  • tenascin R
Topics
  • Adult
  • Biomarkers (blood, cerebrospinal fluid)
  • Brain (metabolism)
  • Brain Injuries, Traumatic (blood, cerebrospinal fluid, metabolism)
  • Extracellular Matrix Proteins (analysis, blood, cerebrospinal fluid)
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurocan (analysis, blood, cerebrospinal fluid)
  • Tenascin (analysis, blood, cerebrospinal fluid)
  • Treatment Outcome

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