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Protein profiling in serum after traumatic brain injury in rats reveals potential injury markers
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-0056-1313
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2018 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 340, p. 71-80Article in journal (Refereed) Published
Abstract [en]

Introduction: The serum proteome following traumatic brain injury (TBI) could provide information for outcome prediction and injury monitoring. The aim with this affinity proteomic study was to identify serum proteins over time and between normoxic and hypoxic conditions in focal TBI. Material and methods: Sprague Dawley rats (n = 73) received a 3 mm deep controlled cortical impact ("severe injury"). Following injury, the rats inhaled either a normoxic (22% O-2) or hypoxic (11% O-2) air mixture for 30 min before resuscitation. The rats were sacrificed at day 1, 3, 7, 14 and 28 after trauma. A total of 204 antibodies targeting 143 unique proteins of interest in TBI research, were selected. The sample proteome was analyzed in a suspension bead array set-up. Comparative statistics and factor analysis were used to detect differences as well as variance in the data. Results: We found that complement factor 9 (C9), complement factor B (CFB) and aldolase c (ALDOC) were detected at higher levels the first days after trauma. In contrast, hypoxia inducing factor (HIF)1 alpha, amyloid precursor protein (APP) and WBSCR17 increased over the subsequent weeks. S100A9 levels were higher in hypoxic-compared to normoxic rats, together with a majority of the analyzed proteins, albeit few reached statistical significance. The principal component analysis revealed a variance in the data, highlighting clusters of proteins. Conclusions: Protein profiling of serum following TBI using an antibody based microarray revealed temporal changes of several proteins over an extended period of up to four weeks. Further studies are warranted to confirm our findings.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 340, p. 71-80
Keywords [en]
Traumatic brain injury, Hypoxia, Serum proteins, Biomarkers, Protein-array
National Category
Neurology
Identifiers
URN: urn:nbn:se:kth:diva-223246DOI: 10.1016/j.bbr.2016.08.058ISI: 000424173400008PubMedID: 27591967Scopus ID: 2-s2.0-85011022724OAI: oai:DiVA.org:kth-223246DiVA, id: diva2:1183768
Funder
VINNOVAKnut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180219

Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2019-01-07Bibliographically approved
In thesis
1. On the profiling of autoantibodies in psychiatric disorders
Open this publication in new window or tab >>On the profiling of autoantibodies in psychiatric disorders
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is a great need to increase our understanding of diseases affecting the brain and their underlying pathogenic mechanisms. To address this need, the work presented in this thesis applied affinity based proteomic techniques to profile proteins, and to investigate protein profiles and the autoantibody repertoire in brain related disorders. Studies included in this thesis cover traumatic brain injuries, first-episode psychosis, schizophrenia and obsessive-compulsive disorders. Paper I describes the profiling of rat serum samples of a traumatic brain injury model to increase the understanding of injury related protein markers and their potential role in patient outcome. Changes in protein profiles over time were characterized as well as potential injury markers related to oxygen intake. Paper II-IV describe the use of protein fragment-based arrays to investigate potential pathogenic autoantibodies associated to the disease. In Paper II possible predictive autoantibodies for the development of schizophrenia were identified, Paper III identified probable brain reactive autoantibodies in schizophrenia patients and Paper IV described the exploration of autoantibodies which might have an association to obsessive-compulsive disorder. Further characterization of these autoantibody repertoires in psychiatric disorders and future efforts could increase our understanding of their role in the associated diseases. Taken together, this work provides the basis for future research in the search for novel disease associated proteins and autoantibody profiles in brain related disorders. An increased understanding and additional diagnostic or prognostic markers of these disorders would be beneficial for both researchers and patients.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2019
Series
TRITA-CBH-FOU ; 2019:3
Keywords
affinity proteomics, microarrays, suspension bead array, autoantibodies, autoimmunity, psychiatric disorders, schizophrenia
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-241047 (URN)978-91-7873-075-9 (ISBN)
Public defence
2019-02-08, Atrium, Nobelsväg 12B, Stockholm, 10:00 (English)
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Note

QC 20180108

Available from: 2019-01-08 Created: 2019-01-07 Last updated: 2019-01-08Bibliographically approved

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Nilsson, Peter

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