Diagnostic PBPK model for S100B

版本 3.0.1 (35.9 MB) 作者: Damir Janigro
This model describes the kinetic behavior of brain-derived biomarkers such as S100B
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更新时间 2022/9/1

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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.
The mp4 file explains the goals and utilizations of this model. Robert Murcko describes how to simulate the model and its fundamental features.

引用格式

Damir Janigro (2022). Diagnostic PBPK model for S100B (https://www.mathworks.com/matlabcentral/fileexchange/106145), MATLAB Central File Exchange. Retrieved February 28, 2022.

Published on line as Murcko R, Marchi N, Bailey D, Janigro D. Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B. Fluids Barriers CNS. 2022;19(1):32. Epub 20220511. doi: 10.1186/s12987-022-00329-9. PubMed PMID: 35546671.

MATLAB 版本兼容性
创建方式 R2021b
兼容 R2022a 及更早的版本
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在 Help Center 和 MATLAB Answers 中查找有关 Neuroscience 的更多信息
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参考作品: Generic SimBiology PBPK model

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版本 已发布 发行说明
3.0.1

Small changes to text
3.0.0

This is a version with a movie explaining how to utilize the model in Simbiology
2.0.2

This updated contains SBML, .MAT, SBPROJ versions of the model. See ReadMeFirst.doc
2.0.1

Contains SBML, SBPROJ, and .MAT files. See ReadMeFirst.doc
2.0.0

Slightly improved version
1.0.0