2017
DOI: 10.1097/aln.0000000000001888
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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

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 actio… Show more

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Cited by 166 publications
(214 citation statements)
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References 52 publications
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“…Plasma hyperosmolality significantly increases CSF influx in anesthetized mice. While the role of the glymphatic pathway both in the clearance (21,28,29,38,41,42) and delivery (21,39,(43)(44)(45)(46)(47)(48) of solutes has been established by multiple groups, prior studies using fluorescent, radiolabeled, and gadolinium-based tracers also suggest that convective flow through this pathway might be exploited to deliver exogenous substances to targets deep within the brain parenchyma. Previous work has shown that the flow of CSF into the brain is increased in circumstances where the brain's volume regulatory capacity is challenged, as occurs with plasma hypertonicity (32).…”
Section: Resultsmentioning
confidence: 99%
“…Plasma hyperosmolality significantly increases CSF influx in anesthetized mice. While the role of the glymphatic pathway both in the clearance (21,28,29,38,41,42) and delivery (21,39,(43)(44)(45)(46)(47)(48) of solutes has been established by multiple groups, prior studies using fluorescent, radiolabeled, and gadolinium-based tracers also suggest that convective flow through this pathway might be exploited to deliver exogenous substances to targets deep within the brain parenchyma. Previous work has shown that the flow of CSF into the brain is increased in circumstances where the brain's volume regulatory capacity is challenged, as occurs with plasma hypertonicity (32).…”
Section: Resultsmentioning
confidence: 99%
“…By using DEXM in conjunction with a relatively low concentration of isoflurane, we attempted to minimize potential experimental confounds arising from anesthesia with pure isoflurane. Furthermore, a DEXM/0.8% isoflurane combination, in contrast to 2% isoflurane, was recently shown to enhance glymphatic transport function and produce 9 -15 Hz spindle oscillations compared with the high concentration isoflurane, thus mirroring a natural sleep state (Benveniste et al, 2017). Physiological parameters, including respiratory rate, oxygen saturation, heart rate, and rectal body temperature, were continuously monitored using an MRIcompatible monitoring system (SA Instruments).…”
Section: Experimental Designmentioning
confidence: 99%
“…State of arousal 46 and type of anesthesia 47 have also been shown to affect GS transport. We did not measure electroencephalogram in the experiments, however anesthetic depth was evaluated indirectly by quantifying anesthetic drugs administered and was found to be similar between strains ( Supplementary Table 1).…”
Section: Mechanisms Underlying the Decreased Gs Transport Chronic Hypmentioning
confidence: 99%
“…Following surgery, the rats were transferred to the MRI instrument. Anesthesia was maintained throughout the experiment by 0.5-1.0% isoflurane in 1:1 Air:O2 mixture delivered via a nose cone, and a subcutaneous infusion of dexmedetomidine (0.015-0.020 mg/kg/hr) 59 . During imaging, respiratory rate, oxygen saturation, body temperature and heart rate were continuously monitored using an MRI compatible monitoring system (SA Instruments, Stony Brook, NY, USA).…”
Section: Anesthesia and Cisterna Magna Cathetermentioning
confidence: 99%
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