Volume 47 Issue 4, April 2026

Cover story:Unlocking brain's drainage: How a metabolic molecule fights stroke swelling. Ischemic stroke often leads to devastating cerebral edema, where fluid buildup compresses the brain. This study reveals that the ketone body beta-hydroxybutyrate (BHB) acts as a potent therapeutic agent by boosting the brain's glymphatic system - its essential waste-clearance pathway. The cover image illustrates the discovered potential mechanism: BHB inhibits HDAC3 and activates p300, which together promote the transcription of α1-syntrophin. This key restoration drives the repolarization of the AQP4 on astrocyte endfeet, enhancing fluid drainage and ultimately alleviating brain edema. The graphic uses green arrows for promotion and red blunt ends for inhibition, mapping the path from metabolic intervention to functional recovery. Doi: 10.1038/s41401-025-01706-4.