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Cited by 236Cerebrospinal fluid and hydrocephalusAnesthesia and Sedative AgentsAnesthesia and Neurotoxicity Research

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Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane

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Benveniste, Helene, Lee, Hedok, Ding, Fengfei, Sun, Qian, Al-Bizri, Ehab, Makaryus, Rany, Probst, Stephen, Nedergaard, Maiken, Stein, Elliot A., Lu, Hanbing·2017·Anesthesiology
DOI 10.1097/aln.0000000000001888PMC PMC5685871
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Abstract

Background: The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not. Methods: Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats. Results: Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats. Conclusions: We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release.

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Metadata

Authors
Benveniste, H., Lee, H., Ding, F., Sun, Q., Al-Bizri, E., Makaryus, R., Probst, S., Nedergaard, M., Stein, E. A., & Lu, H.
Affiliations
  • National Institute on Drug Abuse (US)
  • From the Department of Anesthesiology, Yale School of Medicine, New Haven, Connecticut (H.B., H.L.); Center for Translational Neuromedicine, University of Rochester, Rochester, New York (F.D., Q.S., M.N.); Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York (E.A.-B., R.M., S.P.); National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland (E.A.S., H.L.).
Corresponding author
Benveniste, Helene
ORCID
Venue
Anesthesiology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-12
Volume
127
Issue
6
Pages
976-988
ISSN
0003-3022 (ISSN-L)
DOI
10.1097/aln.0000000000001888
PMC
PMC5685871
OpenAlex
W2757946944
Cited by
236
References
9
Citations by year
2026: 37 · 2025: 33 · 2024: 32 · 2023: 27 · 2022: 30 · 2021: 22 · 2020: 23 · 2019: 18 · 2018: 12 · 2017: 2
FWCI
10.22
Type
journal article
Language
en
Open access
Locations
  • Anesthesiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR001863)
  • National Institute on Aging (RF1AG053991, R01AG048769)
  • National Institute of Neurological Disorders and Stroke (R01NS078304, R01NS100366)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords
dexmedetomidine, isoflurane, cerebrospinal fluid transport, norepinephrine, brain waste clearance, hippocampus, spindle oscillations, cerebral vasculature, contrast-enhanced MRI
MeSH terms
Animals, Biological Transport, Cerebrovascular Circulation, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Hippocampus, Hypnotics and Sedatives, Isoenzymes, Isoflurane, L-Lactate Dehydrogenase, Magnetic Resonance Imaging, Rats, Inbred F344, Signal Transduction, Amyloid beta-Peptides, Anesthetics, Inhalation, Gadolinium DTPA, Dexmedetomidine, Rats

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