Diagnostic Pharmacokinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance - the case of S100B Article Swipe
Robert Murcko
,
Nicola Marchi
,
Damian M. Bailey
,
Damir Janigro
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1277222/v1
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1277222/v1
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 a biomarker’s movement across the body, the sources of a 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 contributed to the uptake of organs of circulating S100B. Additionally, 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.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-1277222/v1
- https://www.researchsquare.com/article/rs-1277222/latest.pdf
- OA Status
- green
- Cited By
- 1
- References
- 37
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4205282524
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4205282524Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-1277222/v1Digital Object Identifier
- Title
-
Diagnostic Pharmacokinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance - the case of S100BWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-01-19Full publication date if available
- Authors
-
Robert Murcko, Nicola Marchi, Damian M. Bailey, Damir JanigroList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-1277222/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-1277222/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-1277222/latest.pdfDirect OA link when available
- Concepts
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Biomarker, Pharmacokinetics, Glymphatic system, Blood–brain barrier, Medicine, Astrocyte, Pathology, Pharmacology, Chemistry, Neuroscience, Central nervous system, Cerebrospinal fluid, Internal medicine, Biology, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2023: 1Per-year citation counts (last 5 years)
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37Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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