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Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B
Blood biomarkers of neurological diseases are often employed to rule out or confirm the presence of significant intracranial or cerebrovascular pathology or for the differential diagnosis of conditions with similar presentations (e.g., hemorrhagic vs. embolic stroke). More widespread utilization of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092835/ https://www.ncbi.nlm.nih.gov/pubmed/35546671 http://dx.doi.org/10.1186/s12987-022-00329-9 |
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author | Murcko, Robert Marchi, Nicola Bailey, Damian Janigro, Damir |
author_facet | Murcko, Robert Marchi, Nicola Bailey, Damian Janigro, Damir |
author_sort | Murcko, Robert |
collection | PubMed |
description | Blood biomarkers of neurological diseases are often employed to rule out or confirm the presence of significant intracranial or cerebrovascular pathology or for the differential diagnosis of conditions with similar presentations (e.g., hemorrhagic vs. embolic stroke). More widespread utilization of biomarkers related to brain health is hampered by our incomplete understanding of the kinetic properties, release patterns, and excretion of molecules derived from the brain. This is, in particular, true for S100B, an astrocyte-derived protein released across the blood–brain barrier (BBB). We developed an open-source pharmacokinetic computer model that allows investigations of biomarker’s movement across the body, the sources of biomarker’s release, and its elimination. This model was derived from a general in silico model of drug pharmacokinetics adapted for protein biomarkers. We improved the model’s predictive value by adding realistic blood flow values, organ levels of S100B, lymphatic and glymphatic circulation, and glomerular filtration for excretion in urine. Three key variables control biomarker levels in blood or saliva: blood–brain barrier permeability, the S100B partition into peripheral organs, and the cellular levels of S100B in astrocytes. A small contribution to steady-state levels of glymphatic drainage was also observed; this mechanism also contributed to the uptake of organs of circulating S100B. This open-source model can also mimic the kinetic behavior of other markers, such as GFAP or NF-L. Our results show that S100B, after uptake by various organs from the systemic circulation, can be released back into systemic fluids at levels that do not significantly affect the clinical significance of venous blood or salivary levels after an episode of BBB disruption. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-022-00329-9. |
format | Online Article Text |
id | pubmed-9092835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90928352022-05-12 Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B Murcko, Robert Marchi, Nicola Bailey, Damian Janigro, Damir Fluids Barriers CNS Research Blood biomarkers of neurological diseases are often employed to rule out or confirm the presence of significant intracranial or cerebrovascular pathology or for the differential diagnosis of conditions with similar presentations (e.g., hemorrhagic vs. embolic stroke). More widespread utilization of biomarkers related to brain health is hampered by our incomplete understanding of the kinetic properties, release patterns, and excretion of molecules derived from the brain. This is, in particular, true for S100B, an astrocyte-derived protein released across the blood–brain barrier (BBB). We developed an open-source pharmacokinetic computer model that allows investigations of biomarker’s movement across the body, the sources of biomarker’s release, and its elimination. This model was derived from a general in silico model of drug pharmacokinetics adapted for protein biomarkers. We improved the model’s predictive value by adding realistic blood flow values, organ levels of S100B, lymphatic and glymphatic circulation, and glomerular filtration for excretion in urine. Three key variables control biomarker levels in blood or saliva: blood–brain barrier permeability, the S100B partition into peripheral organs, and the cellular levels of S100B in astrocytes. A small contribution to steady-state levels of glymphatic drainage was also observed; this mechanism also contributed to the uptake of organs of circulating S100B. This open-source model can also mimic the kinetic behavior of other markers, such as GFAP or NF-L. Our results show that S100B, after uptake by various organs from the systemic circulation, can be released back into systemic fluids at levels that do not significantly affect the clinical significance of venous blood or salivary levels after an episode of BBB disruption. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-022-00329-9. BioMed Central 2022-05-11 /pmc/articles/PMC9092835/ /pubmed/35546671 http://dx.doi.org/10.1186/s12987-022-00329-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Murcko, Robert Marchi, Nicola Bailey, Damian Janigro, Damir Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B |
title | Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B |
title_full | Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B |
title_fullStr | Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B |
title_full_unstemmed | Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B |
title_short | Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B |
title_sort | diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of s100b |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092835/ https://www.ncbi.nlm.nih.gov/pubmed/35546671 http://dx.doi.org/10.1186/s12987-022-00329-9 |
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