In the wake of a stroke, the brain can effectively drown in its own liquids, a new study has revealed. Researchers from the University of Rochester have shown how a stroke can cause the glymphatic system – the brain’s “wastewater” plumbing system – to flood the brain with liquid, causing the brain cells to drown. In turn, this can also increase the chances of cerebral edema, a potentially deadly swelling of the brain seen after some strokes. The phenomenon has only been directly observed in mouse brains so far, however, the researchers hope their discovery could help towards a better understanding of strokes in humans. "Understanding this dynamic – which is propelled by storms of electrical activity in the brain – point the way to potential new strategies that could improve stroke outcomes," Maiken Nedergaard, co-director of the University of Rochester Medical Center and senior author of the article, said in a statement. In 2012, scientists from the University of Rochester's Nedergaard lab were the first to document the discovery of the glymphatic system, a series of pipes hitched onto the brain’s blood vessels that pump cerebrospinal fluid through brain tissue, primarily while we sleep, to help wash away toxic proteins and other waste. Reported in the journal Science, the lab's latest research looked to see whether the glymphatic system is implicated in the brain swelling often seen after an ischemic stroke, the most common form of stroke that occurs when a blood vessel in the brain is blocked. Following a stroke, brain cells become starved of oxygen and nutrients, causing them to erratically “fire off” and depolarize. The electrical waves trigger nearby neurons and spark a wave of electrical hyperactivity in the brain, followed by a wave of inhibition. All of this releases a huge amount of potassium and neurotransmitters in the brain, resulting in the walls of blood vessels to seize up and stopping blood from entering. With the blood vessel now empty, cerebrospinal fluid floods in and brain cells essentially drown. The damage then goes on to cause the brain to swell. “When you force every single cell, which is essentially a battery, to release its charge it represents the single largest disruption of brain function you can achieve – you basically discharge the entire brain surface in one fell swoop,” added Humberto Mestre, a student at the Nedergaard lab and lead author of the study. “The double hit of the spreading depolarization and the ischemia makes the blood vessels cramp, resulting in a level of constriction that is completely abnormal and creating conditions for CSF to rapidly flow into the brain.” While this all sounds pretty grim, the researchers hope their work could be used to reduce the damage caused by strokes, specifically when it comes to cerebral edema. Their study also highlighted the importance of aquaporin 4, a water channel found on cells near the blood-brain barrier that helps to regulate the flow of cerebrospinal fluid. Mice that were genetically engineered to lack aquaporin-4 also experienced a much slower flow of fluid into the brain. Although there’s plenty more to learn about this process, this curious insight could be used to develop interventions that reduce the severity of strokes. Source
