UF Health study alters dogma on cerebrospinal fluid - UF Health

September 5, 2024

By Dorothy Hagmajer

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In this image, the junction of the central nervous system to the peripheral nervous system is seen, as is nanogold accumulated in both the cranial peripheral nerves and spinal nerves. (Photo courtesy of Ed Scott, UF Health)

GAINESVILLE, Fla. — While studying blood stem cells, Edward W. Scott, Ph.D., a professor of molecular genetics and microbiology, discovered something that may change the way scientists understand how cerebrospinal fluid, or CSF, functions in the nervous system.

For 150 years, it has been believed that cerebrospinal fluid — like its name — only circulated in the central nervous system of the brain and spinal cord. Now, after testing his theory in mouse models, Scott and his team confirmed their key finding: cerebral spinal fluid flows all the way from the brain’s spinal cord to the peripheral nervous system. The study was publishedin Science Advances on Wednesday.

“This breaks one of the oldest standing dogmas in neuroscience,” Scott said. “I chalk it up to just paying attention to the things that don’t go the way you expect them to, and then trying to track down what was misunderstood in the first place. It’s where most of the discoveries in my career have come from.”

Originally, researchers were trying to find a means to look at nerves that enter one’s bone marrow, Scott said. Using nanogold particles roughly the size of glucose, a molecule 100,000 times smaller than a standard sheet of paper, researchers infused a tracer dye into the portion of the brain where the vast majority of CSF is produced. The team was able to prove that the nanogold tracer exited the central nervous system and traveled into and throughout peripheral nerves.

“We showed nanogold being delivered within peripheral nerves far down into the leg, including the sciatic nerve,” Scott said.

Importantly, this could result in a more efficient method of drug delivery, allowing patients more relief from less medication. It may help scientists better treat neuropathy, a condition where patients lose feeling in their hands and feet.

Many of the diseases that affect the nervous system — ranging from Parkinson’s to Alzheimer’s and diabetes — result in changes that lead to peripheral neuropathies, where patients begin losing feeling first in their feet, followed by their hands and progressing up their body.

“Any change in the slight pressure up at the top of the system makes really big changes down at your feet,” Scott said. “And it explains why neuropathies start at the extremities and progress inward towards the brain.”

Notably, Scott said, this could impact the way drug delivery systems are modeled. When researchers put dye into the CSF, the nervous system retained it for an extended period of time.

“My own father passed away from Parkinson’s, and I can tell you that when you’re having to take the drugs orally there is a really fine line between getting enough to experience a positive effect versus some of the medications’ negative ones,” Scott said.

If providers were able to input the medication directly into the CSF, patients could have much lower doses, more effectively delivered to the neural tissue the drug is intended to target.

The team will continue working with the mouse model to better define the parameters of how the fluid’s path works in mammals.

“I’m excited to be a part of a discovery that could have such a positive impact,” Scott said.

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