The study by Xie et al. investigates the role of sleep in metabolic homeostasis in the adult brain. Using real-time assessments and two-photon imaging in live mice, the researchers found that natural sleep or anesthesia significantly increase the interstitial space by 60%, leading to enhanced convective exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF). This increased convective flux of ISF improves the clearance of β-amyloid (Aβ), a protein linked to neurodegenerative diseases, during sleep. The findings suggest that the restorative function of sleep may be due to the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system. The study also explores the role of adrenergic signaling in modulating the interstitial space volume and CSF influx, providing insights into the mechanisms underlying the sleep-wake cycle's impact on brain health.The study by Xie et al. investigates the role of sleep in metabolic homeostasis in the adult brain. Using real-time assessments and two-photon imaging in live mice, the researchers found that natural sleep or anesthesia significantly increase the interstitial space by 60%, leading to enhanced convective exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF). This increased convective flux of ISF improves the clearance of β-amyloid (Aβ), a protein linked to neurodegenerative diseases, during sleep. The findings suggest that the restorative function of sleep may be due to the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system. The study also explores the role of adrenergic signaling in modulating the interstitial space volume and CSF influx, providing insights into the mechanisms underlying the sleep-wake cycle's impact on brain health.