Rethinking the Conditions and Mechanism for Glymphatic Clearance

Critical studies that form the foundation of the glymphatic system and the clearance of metabolic by-products of unwanted proteins from the brain are reviewed. Concerns are raised about studying glymphatic flow in anesthetized animals and making assumptions about the whole brain based upon data collected from a cranial window on the cortex. A new model is proposed arguing that the flow of cerebral spinal fluid and parenchymal clearance in the perivascular system of unwanted proteins is regulated by circadian changes in brain temperature and blood flow at the level of the microvasculature.

Summary: Chemical Modulation of Circadian Rhythms and Assessment of Cellular Behavior via Indirubin and Derivatives

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.