Perioperative Medicine  |   December 2017
Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane
Author Notes
  • 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.).
  • This article is featured in “This Month in Anesthesiology,” page 1A.
    This article is featured in “This Month in Anesthesiology,” page 1A.×
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    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication February 27, 2017. Accepted for publication August 16, 2017.
    Submitted for publication February 27, 2017. Accepted for publication August 16, 2017.×
  • Address correspondence to Dr. Benveniste: Department of Anesthesiology, Yale School of Medicine, 333 Cedar Street, TMP3, Rm. 339, New Haven, Connecticut 06520-8089. helene.benveniste@yale.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Basic Science / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   December 2017
Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane
Anesthesiology 12 2017, Vol.127, 976-988. doi:10.1097/ALN.0000000000001888
Anesthesiology 12 2017, Vol.127, 976-988. doi:10.1097/ALN.0000000000001888
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.