Fluid flow in the brain parenchyma during sleep and sedation: a critical test of the glymphatic hypothesis
Author(s)
Miao, Andawei
Type
Thesis
Abstract
The reasons we have to sleep have baffled neuroscientists for decades. A recently proposed glymphatic hypothesis suggested that one of the purposes of sleep is to clean toxic metabolites from the brain during sleep. Since the introduction of this idea, there have been controversies. The glymphatic hypothesis claimed that there is bulk flow in the brain parenchyma that actively sweeps metabolic wastes from the periarterial space towards the perivenous space, and this clearing effect is only turned-on during sleep. However, so far there is not a single published study that has directly tested the movement of fluid in the brain parenchyma which is supposed to be increased during sleep. In this study, a novel method utilising fluorescence recovery after photo-bleaching in combination with a fibre-optic photometry system was developed. This allows an absolute number of diffusion coefficient to be measured in the parenchyma of freely behaving mice. At the same time, a miniature brain activity logger that attached on to the animal skull continuously measures EEG/EMG activity of the brain. Combining these two approaches, fluid flow rates in the brain parenchyma were compared between different vigilance states of the animal and during sedation. The data collected indicated that local fluid flow rate in the frontal cortex of the parenchyma stays unchanged regardless to the vigilance states or sedation by dexmedetomidine and is not affected by circadian time of the day. The results suggested fluid flow in the parenchyma is diffusive. This conclusion does not support the proposed glymphatic hypothesis.
Version
Open Access
Date Issued
2022-06-16
Date Awarded
01/02/2023
License URL
Advisor
Franks, Nicholas
Wisden, William
Sponsor
Wellcome Trust (London, England)
UK Dementia Research Institute
Medical Research Council (Great Britain)
Engineering and Physical Sciences Research Council
Grant Number
107839/Z/15/Z
07841/Z/15/Z
DRI-5004
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)