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Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis
BACKGROUND: The mechanisms of cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP) have not been fully deciphered. One prominent hypothesized mechanism is trans-epithelial water transport mediated by accumulation of solutes at the luminal ChP membrane that produces local osmo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012606/ https://www.ncbi.nlm.nih.gov/pubmed/36915140 http://dx.doi.org/10.1186/s12987-023-00419-2 |
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author | Razzaghi Khamesi, Pooya Charitatos, Vasileios Heerfordt, Eva K. MacAulay, Nanna Kurtcuoglu, Vartan |
author_facet | Razzaghi Khamesi, Pooya Charitatos, Vasileios Heerfordt, Eva K. MacAulay, Nanna Kurtcuoglu, Vartan |
author_sort | Razzaghi Khamesi, Pooya |
collection | PubMed |
description | BACKGROUND: The mechanisms of cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP) have not been fully deciphered. One prominent hypothesized mechanism is trans-epithelial water transport mediated by accumulation of solutes at the luminal ChP membrane that produces local osmotic gradients. However, this standing osmotic gradient hypothesis has not been systematically tested. METHODS: To assess the plausibility of the standing gradient mechanism serving as the main driver of CSF production by the ChP, we developed a three-dimensional (3D) and a one-dimensional (1D) computational model to quantitatively describe the associated processes in the rat ChP inter-microvillar spaces and in CSF pools between macroscopic ChP folds (1D only). The computationally expensive 3D model was used to examine the applicability of the 1D model for hypothesis testing. The 1D model was employed to predict the rate of CSF produced by the standing gradient mechanism for 200,000 parameter permutations. Model parameter values for each permutation were chosen by random sampling from distributions derived from published experimental data. RESULTS: Both models predict that the CSF production rate by the standing osmotic gradient mechanism is below 10% of experimentally measured values that reflect the contribution of all actual production mechanisms. The 1D model indicates that increasing the size of CSF pools between ChP folds, where diffusion dominates solute transport, would increase the contribution of the standing gradient mechanism to CSF production. CONCLUSIONS: The models suggest that the effect of standing osmotic gradients is too small to contribute substantially to CSF production. ChP motion and movement of CSF in the ventricles, which are not accounted for in the models, would further reduce this effect, making it unlikely that standing osmotic gradients are the main drivers of CSF production. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-023-00419-2. |
format | Online Article Text |
id | pubmed-10012606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100126062023-03-15 Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis Razzaghi Khamesi, Pooya Charitatos, Vasileios Heerfordt, Eva K. MacAulay, Nanna Kurtcuoglu, Vartan Fluids Barriers CNS Research BACKGROUND: The mechanisms of cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP) have not been fully deciphered. One prominent hypothesized mechanism is trans-epithelial water transport mediated by accumulation of solutes at the luminal ChP membrane that produces local osmotic gradients. However, this standing osmotic gradient hypothesis has not been systematically tested. METHODS: To assess the plausibility of the standing gradient mechanism serving as the main driver of CSF production by the ChP, we developed a three-dimensional (3D) and a one-dimensional (1D) computational model to quantitatively describe the associated processes in the rat ChP inter-microvillar spaces and in CSF pools between macroscopic ChP folds (1D only). The computationally expensive 3D model was used to examine the applicability of the 1D model for hypothesis testing. The 1D model was employed to predict the rate of CSF produced by the standing gradient mechanism for 200,000 parameter permutations. Model parameter values for each permutation were chosen by random sampling from distributions derived from published experimental data. RESULTS: Both models predict that the CSF production rate by the standing osmotic gradient mechanism is below 10% of experimentally measured values that reflect the contribution of all actual production mechanisms. The 1D model indicates that increasing the size of CSF pools between ChP folds, where diffusion dominates solute transport, would increase the contribution of the standing gradient mechanism to CSF production. CONCLUSIONS: The models suggest that the effect of standing osmotic gradients is too small to contribute substantially to CSF production. ChP motion and movement of CSF in the ventricles, which are not accounted for in the models, would further reduce this effect, making it unlikely that standing osmotic gradients are the main drivers of CSF production. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-023-00419-2. BioMed Central 2023-03-13 /pmc/articles/PMC10012606/ /pubmed/36915140 http://dx.doi.org/10.1186/s12987-023-00419-2 Text en © The Author(s) 2023 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 Razzaghi Khamesi, Pooya Charitatos, Vasileios Heerfordt, Eva K. MacAulay, Nanna Kurtcuoglu, Vartan Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis |
title | Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis |
title_full | Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis |
title_fullStr | Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis |
title_full_unstemmed | Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis |
title_short | Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis |
title_sort | are standing osmotic gradients the main driver of cerebrospinal fluid production? a computational analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012606/ https://www.ncbi.nlm.nih.gov/pubmed/36915140 http://dx.doi.org/10.1186/s12987-023-00419-2 |
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