The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental Methodology

Abstract Cerebrospinal fluid (CSF) dynamics hold implications for neurological health. Despite its importance, accurate quantification of the CSF secretion rate remains a challenge due to methodological controversies and the influence of anesthesia. A novel technique is established to determine CSF...

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Main Authors: Trine L. Toft‐Bertelsen, Beatriche L. Edelbo, Annette B. Steffensen, Sara D. Lolansen, Jonathan H. Wardman, Dennis B. Jensen, Nanna MacAulay
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202412469
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author Trine L. Toft‐Bertelsen
Beatriche L. Edelbo
Annette B. Steffensen
Sara D. Lolansen
Jonathan H. Wardman
Dennis B. Jensen
Nanna MacAulay
author_facet Trine L. Toft‐Bertelsen
Beatriche L. Edelbo
Annette B. Steffensen
Sara D. Lolansen
Jonathan H. Wardman
Dennis B. Jensen
Nanna MacAulay
author_sort Trine L. Toft‐Bertelsen
collection DOAJ
description Abstract Cerebrospinal fluid (CSF) dynamics hold implications for neurological health. Despite its importance, accurate quantification of the CSF secretion rate remains a challenge due to methodological controversies and the influence of anesthesia. A novel technique is established to determine CSF dynamics in awake and freely moving rats, and the CSF secretion is quantified with three different methodologies. The CSF secretion rate is higher in awake rats than in anesthetized rats, the latter demonstrating no requirement for mechanical ventilation for optimal CSF quantification. The CSF secretion rate is ≈10‐fold lower with the “direct method” than with the ventriculo‐cisternal perfusion assay, although the relative acetazolamide‐mediated reduction in CSF secretion is similar across three tested methods. The findings demonstrate the importance of awake models for optimal quantification of the absolute rate of CSF secretion but highlight the versatility of methodologies for the determination of relative changes in CSF secretion associated with inhibitors, age, sex, and various pathologies.
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publishDate 2025-05-01
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spelling doaj-art-e096f5c4c25f4f10aa7f81da7be2b9a22025-08-20T03:48:47ZengWileyAdvanced Science2198-38442025-05-011217n/an/a10.1002/advs.202412469The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental MethodologyTrine L. Toft‐Bertelsen0Beatriche L. Edelbo1Annette B. Steffensen2Sara D. Lolansen3Jonathan H. Wardman4Dennis B. Jensen5Nanna MacAulay6Department of NeuroscienceUniversity of CopenhagenBlegdamsvej 3Copenhagen NDK‐2200DenmarkDepartment of NeuroscienceUniversity of CopenhagenBlegdamsvej 3Copenhagen NDK‐2200DenmarkDepartment of NeuroscienceUniversity of CopenhagenBlegdamsvej 3Copenhagen NDK‐2200DenmarkDepartment of NeuroscienceUniversity of CopenhagenBlegdamsvej 3Copenhagen NDK‐2200DenmarkDepartment of NeuroscienceUniversity of CopenhagenBlegdamsvej 3Copenhagen NDK‐2200DenmarkDepartment of NeuroscienceUniversity of CopenhagenBlegdamsvej 3Copenhagen NDK‐2200DenmarkDepartment of NeuroscienceUniversity of CopenhagenBlegdamsvej 3Copenhagen NDK‐2200DenmarkAbstract Cerebrospinal fluid (CSF) dynamics hold implications for neurological health. Despite its importance, accurate quantification of the CSF secretion rate remains a challenge due to methodological controversies and the influence of anesthesia. A novel technique is established to determine CSF dynamics in awake and freely moving rats, and the CSF secretion is quantified with three different methodologies. The CSF secretion rate is higher in awake rats than in anesthetized rats, the latter demonstrating no requirement for mechanical ventilation for optimal CSF quantification. The CSF secretion rate is ≈10‐fold lower with the “direct method” than with the ventriculo‐cisternal perfusion assay, although the relative acetazolamide‐mediated reduction in CSF secretion is similar across three tested methods. The findings demonstrate the importance of awake models for optimal quantification of the absolute rate of CSF secretion but highlight the versatility of methodologies for the determination of relative changes in CSF secretion associated with inhibitors, age, sex, and various pathologies.https://doi.org/10.1002/advs.202412469acetazolamideCSFCSF measurementsdirect methodventriculo‐cisternal perfusion assay
spellingShingle Trine L. Toft‐Bertelsen
Beatriche L. Edelbo
Annette B. Steffensen
Sara D. Lolansen
Jonathan H. Wardman
Dennis B. Jensen
Nanna MacAulay
The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental Methodology
Advanced Science
acetazolamide
CSF
CSF measurements
direct method
ventriculo‐cisternal perfusion assay
title The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental Methodology
title_full The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental Methodology
title_fullStr The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental Methodology
title_full_unstemmed The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental Methodology
title_short The Cerebrospinal Fluid Secretion Rate Increases in Awake and Freely Moving Rats but Differs With Experimental Methodology
title_sort cerebrospinal fluid secretion rate increases in awake and freely moving rats but differs with experimental methodology
topic acetazolamide
CSF
CSF measurements
direct method
ventriculo‐cisternal perfusion assay
url https://doi.org/10.1002/advs.202412469
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