A Highly Predictive MicroRNA Panel for Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage

Authors

Wang-Xia Wang, University of KentuckyFollow
Joe E. Springer, University of KentuckyFollow
Kevin Xie, University of KentuckyFollow
David W. Fardo, University of KentuckyFollow
Kevin W. Hatton, University of KentuckyFollow

Abstract

Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3–10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without DCV at 3 and 7 days after aSAH, as well as from eight healthy controls. The analysis of the first 18-patient cohort revealed a striking differential expression pattern of the selected miRNAs in CSF and plasma of aSAH patients with DCV from those without DCV. Importantly, this differential expression was observed at the early time point (3 days after aSAH), before DCV event occurs. Seven miRNAs were identified as reliable DCV risk predictors along with a prediction model constructed based on an array of additional 19 miRNAs on the panel. These chosen miRNAs were then used to predict the risk of DCV in a separate, testing cohort of 15 patients. The accuracy of DCV risk prediction in the testing cohort reached 87%. The study demonstrates that our novel designed miRNA panel is an effective predictor of DCV risk and has strong applications in clinical management of aSAH patients.

Document Type

Article

Publication Date

5-14-2021

Notes/Citation Information

Published in Frontiers in Molecular Biosciences, v. 8, article 657258.

© 2021 Wang, Springer, Xie, Fardo and Hatton

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Digital Object Identifier (DOI)

https://doi.org/10.3389/fmolb.2021.657258

Funding Information

This work was supported by Grants 15-12A and 18-8A from the Kentucky Spinal Cord and Head Injury Research Trust (WXW and JES) and an endowment from the Kentucky Spinal Cord and Head Injury Research Trust (JS). Healthy control specimens were obtained from the University of Kentucky Alzheimer’s Disease Center (UK-ADC), supported by NIH Grant P30 AG280303.

Related Content

The data presented in the study are deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession number GSE165608.

Repository Citation

Wang, Wang-Xia; Springer, Joe E.; Xie, Kevin; Fardo, David W.; and Hatton, Kevin W., "A Highly Predictive MicroRNA Panel for Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage" (2021). Sanders-Brown Center on Aging Faculty Publications. 169.
https://uknowledge.uky.edu/sbcoa_facpub/169