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2017 ; 127
(6
): 976-988
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English Wikipedia
Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute
Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose
Isoflurane
#MMPMID28938276
Benveniste H
; Lee H
; Ding F
; Sun Q
; Al-Bizri E
; Makaryus R
; Probst S
; Nedergaard M
; Stein EA
; Lu H
Anesthesiology
2017[Dec]; 127
(6
): 976-988
PMID28938276
show ga
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.