Minta, K;
Brinkmalm, G;
Thelin, EP;
Al Nimer, F;
Piehl, F;
Tullberg, M;
Jeppsson, A;
... Andreasson, U; + view all
(2021)
Cerebrospinal fluid brevican and neurocan fragment patterns in human traumatic brain injury.
Clinica Chimica Acta
, 512
pp. 74-83.
10.1016/j.cca.2020.11.017.
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Abstract
BACKGROUND: Altered levels of two extracellular matrix (ECM) proteoglycans, brevican and neurocan, have been found in brain injury models; however, their proteolytic processing in traumatic brain injury (TBI) remains unexplored. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a possible contributor to ECM remodelling following TBI. The aims of this study were to evaluate proteolytic brevican/neurocan patterns and ADAMTS-like activity in cerebrospinal fluid (CSF) in the context of TBI. MATERIALS AND METHODS: Forty-two acute TBI patients and 37 idiopathic normal pressure hydrocephalus (iNPH) patients were included in the analysis of tryptic brevican and neurocan peptides in CSF using parallel reaction monitoring mass spectrometry. Twenty-nine TBI and 36 iNPH patients were analysed for ADAMTS-like activity in CSF using a quenched fluorescent substrate. RESULTS: The majority of CSF concentrations of brevican peptides significantly decreased in TBI patients compared with the iNPH group (p ≤ 0.002), while ADAMTS-like activity increased (p < 0.0001). Two C-terminal brevican peptides strongly correlated with unfavourable outcome of TBI patients (rho = 0.85-0.93, p ≤ 0.001). CONCLUSIONS: The decreased CSF concentrations of brevican peptides in TBI are associated with their increased degradation by ADAMTS enzymes. Furthermore, the N- and C-terminal parts of brevican are differentially regulated following TBI and may serve as outcome markers.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid brevican and neurocan fragment patterns in human traumatic brain injury |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.cca.2020.11.017 |
| Publisher version: | https://doi.org/10.1016/j.cca.2020.11.017 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | Brevican, Cerebrospinal fluid, Idiopathic normal pressure hydrocephalus, Neurocan, Parallel reaction monitoring mass spectrometry, traumatic brain injury |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10118870 |
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