Significance of Understanding Function of Glymphatic System to Manage Practical Clinical Problems of the Elderly

The effect of photobiomodulation on the brain during wakefulness and sleep

“…Although the precise function of sleep is not clear, it has been suggested recently to be the critical period of the 24 h cycle when the brain replenishes its resident fluid and clears all of its cellular debris and waste-products before they become toxic; that sleep is when the brain assumes a house-keeping function, a function that it cannot undertake readily during wakefulness, when it is fully occupied with orchestrating all the complex neural networks associated with the executive functions, namely cognition, attention, memory and skilled movements ( Iliff et al, 2012 ; Rasch and Born, 2013 ; Aspelund et al, 2015 ; Eugene and Masiak, 2015 ; Jessen et al, 2015 ; Louveau et al, 2015 , 2017 ; Brodziak et al, 2018 ; Plog and Nedergaard, 2018 ; Hablitz et al, 2020 ; Mestre et al, 2020 ; Nedergaard and Goldman, 2020 ; Reddy and van der Werf, 2020 ; Yan et al, 2021 ). Recent studies have reported that both children and adults are able to retain memories better after they slept well.…”

“…Cerebrospinal fluid flows into perivascular spaces around the arteries and then into the interstitial space within the brain via water channels (aquaporin-4) in astrocytic end-feet. This process then drives the drainage of excess fluid and waste within the interstitial space out and into perivascular spaces around the veins, disposing ultimately through lymphatic vessels through the meninges and then down into the venous system ( Iliff et al, 2012 ; Rasch and Born, 2013 ; Aspelund et al, 2015 ; Eugene and Masiak, 2015 ; Jessen et al, 2015 ; Louveau et al, 2015 , 2017 ; Brodziak et al, 2018 ; Plog and Nedergaard, 2018 ; Hablitz et al, 2020 ; Mestre et al, 2020 ; Nedergaard and Goldman, 2020 ; Reddy and van der Werf, 2020 ; Yan et al, 2021 ).…”

“…The activity of the glymphatic system is much greater in the state of sleep ( Figure 3C ) than in wakefulness ( Figure 3B ). Its activity has been shown to be correlated tightly with changes in brain wave-forms in the different arousal states; it increases with the onset and predominance of δ and θ waves, characteristic of slow-wave, non-rapid eye movement sleep and reduces with the onset and predominance of α and β waves, characteristic of wakefulness (and rapid-eye movement sleep) ( Iliff et al, 2012 ; Rasch and Born, 2013 ; Aspelund et al, 2015 ; Eugene and Masiak, 2015 ; Jessen et al, 2015 ; Louveau et al, 2015 , 2017 ; Brodziak et al, 2018 ; Plog and Nedergaard, 2018 ; Hablitz et al, 2020 ; Mestre et al, 2020 ; Nedergaard and Goldman, 2020 ; Reddy and van der Werf, 2020 ; Yan et al, 2021 ).…”

“…In Alzheimer’s disease for example, there are many reports that the activity of the glymphatic system is very much reduced ( Figures 4A,B ). In mouse models of the disease, there is reduced glymphatic influx, resulting in less clearance of the β-amyloid ( Iliff et al, 2012 ; Rasch and Born, 2013 ; Aspelund et al, 2015 ; Eugene and Masiak, 2015 ; Jessen et al, 2015 ; Louveau et al, 2015 , 2017 ; Brodziak et al, 2018 ; Plog and Nedergaard, 2018 ; Hablitz et al, 2020 ; Mestre et al, 2020 ; Nedergaard and Goldman, 2020 ; Reddy and van der Werf, 2020 ; Yan et al, 2021 ) and tau proteins ( Harrison et al, 2020 ).…”

“…In this state, the brain assumes a house-keeping function, disposing of all the metabolic debris and waste-products that have accumulated during the day before they reach toxic levels. This fluid-mediated detoxification is under circadian control ( Iliff et al, 2012 ; Aspelund et al, 2015 ; Eugene and Masiak, 2015 ; Jessen et al, 2015 ; Louveau et al, 2015 , 2017 ; Brodziak et al, 2018 ; Plog and Nedergaard, 2018 ; Hablitz et al, 2020 ; Mestre et al, 2020 ; Nedergaard and Goldman, 2020 ; Reddy and van der Werf, 2020 ; Yan et al, 2021 ).…”