Proteomic changes in intracranial blood during human ischemic stroke

Benton Maglinger, Jacqueline A. Frank, Christopher J. McLouth, Amanda L. Trout, Jill Marie Roberts, Stephen Grupke, Jadwiga Turchan-Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background Since 2015, mechanical thrombectomy has been the standard treatment for emergent large vessel occlusion ischemic stroke. Objective To investigate, using the previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683), how the protein expression of a patient's intracranial blood during ischemic stroke compares with the protein expression of their systemic arterial blood in order to better understand and treat stroke. Methods Plasma samples from 25 subjects underwent proteomic analysis, where intracranial protein expression was compared with systemic protein levels. Data including sex, comorbidities, infarct volume, and infarct time were included for each subject. Results A majority of important proteins had a lower expression in intracranial blood than in systemic arterial blood. Proteins with the most significant changes in expression were: endopeptidase at -0.26 (p<0.0001), phospholipid transfer protein (PLTP) at -0.26 (p=0.0005), uromodulin (UMOD) at -0.14 (p=0.002), ficolin-2 (FCN2) at -0.46 (p=0.005), C-C motif chemokine 19 (CCL19) at -0.51 (p<0.0001), C-C motif chemokine 20 (CCL20) at -0.40 (p<0.0001), fibroblast growth factor 21 at -0.37 (p=0.0002), and C-C motif chemokine (CCL23) at -0.43 (p=0.0003). Conclusions Evaluation of proteomic changes in the intravascular space of a cerebral infarct in progress in human subjects suggested that changes in proteins such PLTP, fetuin-B (FETUB), and FCN2 may be involved in atherosclerotic changes, and chemokines such as CCL23 are known to play a role in the Th2 autoimmune response. These data provide a scientific springboard for identifying clinically relevant biomarkers for diagnosis/prognosis, and targets for much needed neuroprotective/neuroreparative pharmacotherapies.

Original languageEnglish
Pages (from-to)395-399
Number of pages5
JournalJournal of NeuroInterventional Surgery
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2021

Bibliographical note

Funding Information:
Acknowledgements The project described was supported by the National Center for Advancing Translational Sciences, through grant UL1TR001998 and UKHealthCare. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Contributors Conception and design of study: JFF, KRP. Acquisition and analysis of data: BM, JAF, CJM, JFF, SG, ALT, JMR, JT-C, AMS, KRP. Drafting a significant portion of the manuscript: BM, JAF, CJM, AMS, JFF, KRP. Funding Funding from UK Center for Clinical and Translational Science (CCTS). Competing interests Authors KRP, AMS, and JFF are co-founders/equity holders in Cerelux, LLC. Patient consent for publication Not required. ethics approval University of Kentucky Medical institutional review board: 48831. Provenance and peer review Not commissioned; externally peer reviewed. data availability statement Data are available upon request. Please contact the corresponding author (KRP) for details. Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Keywords

  • artery
  • stroke
  • thrombectomy

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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