Proteomic changes in intracranial blood during human ischemic stroke

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.

Keywords: artery; stroke; thrombectomy.