Brain’s other plumbing system plays role in both good health and response to injury

Tracing the flow of cerebrospinal fluid.

Swelling occurs whenever the organs, skin, or other parts of your body enlarge. It’s typically the result of inflammation or a buildup of fluid.

Doctors have long known about the dangers of swelling. A new has suggests that the brain’s other plumbing system, which circulates cerebrospinal fluid (CSF), may play an underappreciated role in both good health and response to injury.

Cerebrospinal fluid (CSF) is a clear fluid that surrounds the brain and spinal cord. It cushions the brain and spinal cord from injury and also serves as nutrient delivery and waste removal system for the brain.

Douglas Kelley, a mechanical engineer at the University of Rochester in collaboration with Rochester neuroscientist Maiken Nedergaard, demonstrated the early swelling immediately after an injury or stroke results not from blood but an inrush of CSF.

Kelley said, “There is this whole other fluid transport system beyond blood. It matters for disease and pathology, and it matters for drug delivery.”

It was assumed that the CSF only flows around the brain tissue. In 2012, Nedergaard’s group presented a study- demonstrating the existence of CSF pathways through the brain. The research also suggests that CSF flows along these glymphatic pathways during sleep and rinses away cellular debris, like the amyloid-beta and tau proteins that accumulate and have been linked to Alzheimer’s disease.

Kelley said, “They let us make predictions about the speed of flow, and when the flow is more important, and when diffusion is more important. We can make better predictions now than anybody could three or four years ago.”

Saikat Mukherjee, a postdoctoral researcher at the University of Minnesota, noted, “Scientists still disagree about whether or not CSF enters brain tissue. If it doesn’t, then the brain primarily relies on diffusion to clear toxic proteins. If CSF does seep into the brain tissue, even a little, then advection—the clearing of material by fluid flow—could help significantly with the cleanup.”

“The difference may be huge. Toxic proteins get released from the brain and don’t just sit there. They aggregate into higher and higher molecular weight proteins.”

Mukherjee’s work proposes that diffusion isn’t as proficient in clearing larger aggregates, while advection may remove any size proteins.

If advection does turn out to play a role, then perhaps that knowledge could be harnessed to develop new neurodegenerative disease treatments that better clear protein aggregates.

Scientists are now investigating clinical data on plaque buildup in the brain to see how well it matches their simulations. They’re additionally evaluating discoveries from studies researching the clearance of toxic proteins during the sleep-wake cycle.

He noted, “Ultimately, using fluid dynamics to study brain fluids points opens up two clear pathways of research. First, it can help neuroscientists better understand how the body gets rid of cellular debris—and what happens, from a physics point of view, when that system breaks down. Second, it could lead to insights on more fundamental questions about fluid dynamics and reaction-diffusion transport mechanisms in the brain.”

“It lets us look at new physics that no one else has looked at yet.”

The work is presented at the 73rd Annual Meeting of the American Physical Society’s Division of Fluid Dynamics.

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