Mechanisms of Activation of Brain's Drainage During Sleep: The Nightlife of Astrocytes

The study of functions, mechanisms of generation, and pathways of movement of cerebral fluids has a long history, but the last decade has been especially productive. The proposed glymphatic hypothesis, which suggests a mechanism of the brain waste removal system (BWRS), caused an active discussion on both the criticism of some of the perspectives and our intensive study of new experimental facts. It was especially found that the intensity of the metabolite clearance changes significantly during the transition between sleep and wakefulness. Interestingly, at the cellular level, a number of aspects of this problem have been focused on, such as astrocytes-glial cells, which, over the past two decades, have been recognized as equal partners of neurons and perform many important functions. In particular, an important role was assigned to astrocytes within the framework of the glymphatic hypothesis. In this review, we return to the "astrocytocentric" view of the BWRS function and the explanation of its activation during sleep from the viewpoint of new findings over the last decade. Our main conclusion is that the BWRS's action may be analyzed both at the systemic (whole-brain) and at the local (cellular) level. The local level means here that the neuro-glial-vascular unit can also be regarded as the smallest functional unit of sleep, and therefore, the smallest functional unit of the BWRS.