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Cited by 190Cerebrospinal fluid and hydrocephalusAdvanced MRI Techniques and ApplicationsTraumatic Brain Injury and Neurovascular Disturbances

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General Anesthesia Inhibits the Activity of the “Glymphatic System”

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Gakuba, Clement, Gaberel, Thomas, Goursaud, Suzanne, Bourges, Jennifer, Di Palma, Camille, Quenault, Aurélien, de Lizarrondo, Sara Martinez, Vivien, Denis, Gauberti, Maxime·2018·Theranostics
DOI 10.7150/thno.19154PMC PMC5771087
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Abstract

INTRODUCTION:According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF).Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space.Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation.METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice.RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation.Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia.This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane).These results were consistent across the different anesthesia regimens and imaging modalities.Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION:The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness.General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.

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  • Almost all experiments that have been interpreted as showing that sleep or anesthesia change brain clearance have involved introducing markers into the CSF, which then move into the brain parenchyma, confounding quantification of clearance.

    “Indeed, almost all the experiments that have been interpreted as showing that sleep or anesthesia change brain clearance have involved introducing markers into the CSF, which then move into the brain parenchyma14,26–30. Under these circumstances, entry, exit and redistribution of the marker are all occurring simultaneously, greatly confounding any quantification of clearance.”

    From Brain clearance is reduced during sleep and anesthesia (2024) · cites this paper as [28]

    The Discussion (page unavailable) says this study and previous studies introduced tracers into the CSF and measured their influx into brain tissue. It also raises methodological concerns about tracer injection. It does not establish that almost all sleep- or anesthesia-related clearance experiments used this approach, or say that simultaneous entry, exit, and redistribution confound clearance measurements. (LLM, conf=0.84)

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Metadata

Authors
Gakuba, C., Gaberel, T., Goursaud, S., Bourges, J., Di Palma, C., Quenault, A., de Lizarrondo, S. M., Vivien, D., & Gauberti, M.
Affiliations
Inserm (FR)
Corresponding author
Gauberti, Maxime
ORCID
Venue
Theranostics
Publisher
Ivyspring International Publisher
Published
2018
Volume
8
Issue
3
Pages
710-722
ISSN
1838-7640 (ISSN-L)
DOI
10.7150/thno.19154
PMC
PMC5771087
OpenAlex
W2769041798
Cited by
190
References
11
Citations by year
2026: 31 · 2025: 19 · 2024: 22 · 2023: 27 · 2022: 15 · 2021: 26 · 2020: 18 · 2019: 18 · 2018: 13
FWCI
9.29
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Theranostics (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Fondation pour la Recherche Médicale
Topics
  • Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
glymphatic system, general anesthesia, cerebrospinal fluid flow, brain waste clearance, isoflurane, ketamine, extracellular space, wakefulness, in vivo brain imaging, mice
MeSH terms
Glymphatic System, Anesthesia, General, Animals, Contrast Media, Fluorescent Dyes, Magnetic Resonance Imaging, Male, Anesthetics, Inhalation, Spectroscopy, Near-Infrared, Mice

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