Hm (though this only applies for anesthetic doses and not as much for recreational ones).
State of Arousal
One of the most exciting studies concerning the glymphatic pathway was the report of the enhancing effect of sleep on influx and clearance of waste solutes including Aβ. Thus, in rodents, glymphatic influx was increased by 95% and Aβ was cleared 2-fold faster in the cortex during slow wave sleep (or anesthesia with ketamine/xylazine) when compared to wakefulness [7]. Because sleep is associated with improved brain waste clearance when compared to wakefulness, it is inferred that all drug-induced low arousal/sleep states will promote brain waste clearance. However, the basis for sleep-induced enhancement of glymphatic transport appears to be closely linked to central norepinephrine tone/activity. In agreement with this concept, we recently showed that rats receiving dexmedetomidine (which blocks norepinephrine release from the locus coeruleus) in combination with low-dose isoflurane exhibit a 30% higher glymphatic transport function relative to rats receiving isoflurane alone [62]. This finding may be important for clinical practice because dexmedetomidine or other drugs that reduce central norepinephrine signaling could have the added benefit of improving “brain waste removal” during anesthesia and surgery. The beneficial effect of dexmedetomidine in the context of glymphatic transport might also explain why the use of dexmedetomidine decreases the incidence of postoperative delirium [63].
Regional brain clearance is strongly organised and broadly consistent across individuals. It is among the fastest in the entorhinal cortex, where tau pathology typically first appears, and declines across the Braak hierarchy.
Just one night of sleep deprivation was associated with approximately one-third lower clearance across the brain, while the regional pattern remained largely unchanged.
The overall clearance level and its spatial pattern play distinct roles in simulated tau propagation. Using these estimated clearance maps in a mathematical model of tau spreading across the connectome, we found that the overall clearance level sets the pace of simulated pathology, while the spatial pattern of clearance modifies local vulnerability and the course of progression.