McKelvey School of Engineering

Insight into brain’s waste clearing system may shed light on brain diseases

This microscopic image reveals the enhanced glymphatic transport of an intranasally delivered tracer (red), achieved using ultrasound combined with microbubbles. (Credit: Chen Lab)

Like the lymphatic system in the body, the glymphatic system in the brain clears metabolic waste and distributes nutrients and other important compounds. Impairments in this system may contribute to brain diseases, such as neurodegenerative diseases and stroke.

A team of researchers in the McKelvey School of Engineering at Washington University in St. Louis has found a noninvasive and nonpharmaceutical method to influence glymphatic transport using focused ultrasound, opening the opportunity to use the method to further study brain diseases and brain function. Results of the work are published in the Proceedings of the National Academy of Sciences May 15.

Hong Chen, PhD, associate professor of biomedical engineering in McKelvey Engineering and of neurological surgery in the School of Medicine, and her team, including Dezhuang (Summer) Ye, a postdoctoral research associate, and Si (Stacie) Chen, a former postdoctoral research associate, found the first direct evidence that focused ultrasound, combined with circulating microbubbles — a technique they call FUSMB — could mechanically enhance glymphatic transport in the mouse brain.

Chen

Focused ultrasound can penetrate the scalp and skull to reach the brain and precisely target a defined region within the brain. In previous work, Chen’s team found that microbubbles injected into the bloodstream amplify the effects of the ultrasound waves on the blood vessels and generate a pumping effect, which helps with the accumulation of intranasally delivered agents in the brain, such as drugs or gene therapy treatments.

“Intranasal delivery provides a novel, noninvasive route to investigate the glymphatic pathway in intact brains,” Chen said. “This route for investigating glymphatic transport has the potential to be utilized in the study of glymphatic function in humans, which is currently limited by the absence of noninvasive approaches to access the glymphatic system.”

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