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World J Neurol. Aug 30, 2022; 8(1): 1-9
Published online Aug 30, 2022. doi: 10.5316/wjn.v8.i1.1
Role of cell-free DNA for predicting incidence and outcome of patients with ischemic stroke
Nusrath Fathima, Sandhya Manorenj, Sandeep Kumar Vishwakarma, Aleem Ahmed Khan
Nusrath Fathima, Sandeep Kumar Vishwakarma, Aleem Ahmed Khan, Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India
Sandhya Manorenj, Department of Neurology, Princess Esra Hospital, Deccan College of Medical Sciences, Hyderabad 500002, Telangana, India
Author contributions: Fathima N, Manorenj S, Vishwakarma SK and Khan AA performed literature search, collected the data and wrote the manuscript; Fathima N and Vishwakarma SK formatted and revised the manuscript; Manorenj S provided clinical inputs; Khan AA shared his relevant experience; Vishwakarma SK and Khan AA edited the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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 and the use is non-commercial. See:
Corresponding author: Aleem Ahmed Khan, PhD, Scientist and Head, Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, DMRL X Road, Hyderabad 500058, Telangana, India.
Received: January 11, 2022
Peer-review started: January 11, 2022
First decision: May 31, 2022
Revised: June 11, 2022
Accepted: July 27, 2022
Article in press: July 27, 2022
Published online: August 30, 2022

Early diagnosis and prognosis of ischemic stroke remains a critical challenge in clinical settings. A blood biomarker can be a promising quantitative tool to represent the clinical manifestations in ischemic stroke. Cell-free DNA (cfDNA) has recently turned out to be a popular circulating biomarker due to its potential relevance for diagnostic applications in a variety of disorders. Despite bright outlook of cfDNA in clinical applications, very less is known about its origin, composition, or function. Several recent studies have identified cell-derived mitochondrial components including mitochondrial DNA (mtDNA) in the extracellular spaces including blood and cerebrospinal fluid. However, the time course of alterations in plasma mtDNA concentrations in patients after an ischemic stroke is poorly understood. DNA is thought to be freed into the plasma shortly after the commencement of an ischemic stroke and then gradually decreased. However, the importance of cell-free mtDNA (cf-mtDNA) in ischemic stroke is still unknown. This review summarizes about the utility of biomarkers which has been standardized in clinical settings and role of cfDNA including cf-mtDNA as a non-invasive potential biomarker of ischemic stroke.

Keywords: Ischemic stroke, Mitochondria, Circulating cell-free DNA, Plasma nucleic acid, Mortality

Core Tip: Early and accurate diagnosis of ischemic stroke is critical to achieve favorable clinical outcome. Cell-free DNA can be used as a useful biomarker for early diagnosis and prognosis of ischemic stroke for saving time and increasing the likelihood of successful intervention. Discriminative quantification of cell free mitochondrial DNA instead of overall circulating DNA may provide more significant value for identifying real-time host response. The future practical adoption of this strategy may be aided by reliable and standardized quantification of cell-free mitochondrial DNAs in ischemic stroke patients to design more effective diagnosis, prognosis and therapeutic strategies.