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Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys
A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773283/ https://www.ncbi.nlm.nih.gov/pubmed/33378399 http://dx.doi.org/10.1371/journal.pone.0244090 |
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author | Khani, Mohammadreza Fu, Audrey Q. Pluid, Joshua Gibbs, Christina P. Oshinski, John N. Xing, Tao Stewart, Gregory R. Zeller, Jillynne R. Martin, Bryn A. |
author_facet | Khani, Mohammadreza Fu, Audrey Q. Pluid, Joshua Gibbs, Christina P. Oshinski, John N. Xing, Tao Stewart, Gregory R. Zeller, Jillynne R. Martin, Bryn A. |
author_sort | Khani, Mohammadreza |
collection | PubMed |
description | A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there was a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with cervical implantation compared to lumbar implantation. CSF flow rate decreased up to 55% with the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation in Cynomolgus monkeys. |
format | Online Article Text |
id | pubmed-7773283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77732832021-01-07 Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys Khani, Mohammadreza Fu, Audrey Q. Pluid, Joshua Gibbs, Christina P. Oshinski, John N. Xing, Tao Stewart, Gregory R. Zeller, Jillynne R. Martin, Bryn A. PLoS One Research Article A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there was a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with cervical implantation compared to lumbar implantation. CSF flow rate decreased up to 55% with the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation in Cynomolgus monkeys. Public Library of Science 2020-12-30 /pmc/articles/PMC7773283/ /pubmed/33378399 http://dx.doi.org/10.1371/journal.pone.0244090 Text en © 2020 Khani et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Khani, Mohammadreza Fu, Audrey Q. Pluid, Joshua Gibbs, Christina P. Oshinski, John N. Xing, Tao Stewart, Gregory R. Zeller, Jillynne R. Martin, Bryn A. Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys |
title | Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys |
title_full | Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys |
title_fullStr | Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys |
title_full_unstemmed | Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys |
title_short | Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys |
title_sort | intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773283/ https://www.ncbi.nlm.nih.gov/pubmed/33378399 http://dx.doi.org/10.1371/journal.pone.0244090 |
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