What ‘drives’ the brain’s waste disposal system?

Jessica Shang will use her CAREER award to find answers with computational modeling

Groundbreaking University of Rochester research discovered that the brain’s glymphatic system is a remarkable waste disposal system.

With support of a prestigious National Science Foundation CAREER award, Jessica Shang, assistant professor of mechanical engineering at Rochester, will create a computational model to determine what actually “drives” the system and helps it flush away metabolic wastes linked to Alzheimer’s and other neurodegenerative diseases.

“Fully understanding the mechanics of fluid flow in the brain will advance our capabilities to correlate age-related ailments with neurodegeneration, predict patient outcomes, and drive treatment and prevention strategies,” Shang says.

She will collaborate with Maiken Nedergaard, co-director of the University’s Center for Translational Neuromedicine, who was the first to describe the glymphatic system. Subsequent research by Nedergaard’s team and colleagues revealed that the waste removal system is more active while we sleep and can be damaged by stroke and trauma.

The link between blood vessels and the flow of cerebrospinal fluid

Shang will build on discoveries resulting from a recent collaboration between Nedergaard, and mechanical engineering faculty members Douglas Kelley and Jack Thomas. The engineers used an automated particle tracking code previously developed by Kelley’s lab to trace the movements of tiny particles injected into the cerebrospinal fluid of mice.

They discovered that the flow of cerebrospinal fluid, which passes through the perivascular spaces that surround arteries in the brain’s membrane, is synchronized with heart beats.

“Because your blood vessels are elastic, the blood pulsing through them creates a traveling wave along the wall of the vessels,” Shang says. “These moving walls of the blood vessels help push the cerebrospinal fluid through the perivascular space—basically a ring that surrounds the blood vessels.”

This supports a hypothesis that the glymphatic system is primarily, perhaps even entirely driven by the flexing of arterial walls. But so far, experimental observations of this phenomenon have been limited to the outer surfaces of the brain.

“We don’t have a very good understanding of the evolution of the wave that travels from your heart to the various vessels throughout the brain, and how that links to the cerebrospinal fluid flow,” Shang says.

She proposes creating a computational model, “which encompasses this branching network on both the blood and cerebrospinal side,” to simulate the systemwide interaction of cerebrospinal fluid and blood flow throughout the brain.

To avoid the excessive time and computational power that would be needed to do this in 3D, Shang will instead use 1D wave models to capture the basic properties of the system that affect how the wall wave moves, such as stiffness and diameter. The model’s parameters can then be manipulated to mimic vascular conditions that result from high blood pressure or transient spikes in neural activity.

Experimental data from Nedergaard’s lab will help refine the model, Shang says.

Working with Upward Bound students to broaden the impact

The Faculty Early Career Development (CAREER) award is NSF’s most prestigious recognition for early-career faculty members. It provides recipients with five years of funding to help lay the foundation for their future research. It also requires recipients to demonstrate how their research can have a broader educational impact.

Shang is working with the University’s David T. Kearns Center to devise a way for Upward Bound students from the Rochester City School district to work alongside mechanical engineering students on hands-on projects in a fluids lab course she teaches to juniors.

“By having the Upward Bound students interact with juniors,” she says, “they’ll get a good sense of what a mechanical engineer can actually do.”