FIGURE 3.

During brain activation and information processing, ISF enters active astrocytes via AQP-4 channels, leaving less fluid in the extracellular space and upregulating lactate (shuttled to neurons). During idle time or slow wave sleep, ISF exits the astrocyte, widening the extracellular space and lowering lactate to facilitate waste clearance. To accomplish their physiological functions, astrocytes require activation by BDNF. Senescent cerebral ECs produce less BDNF, probably leading to astrocyte deactivation and dysfunctional glymphatic clearance.