Introducing the brain: the brain's cleaning fluid (Introduction)

by David Turell , Wednesday, March 26, 2025, 18:41 (7 days ago) @ David Turell

Cerebrospinal fluid is a mysterious aspect of the brain:

https://www.quantamagazine.org/the-mysterious-flow-of-fluid-in-the-brain-20250326/

"Incased in the skull, perched atop the spine, the brain has a carefully managed existence. It receives only certain nutrients, filtered through the blood-brain barrier; an elaborate system of protective membranes surrounds it. That privileged space contains a mystery. For more than a century, scientists have wondered: If it’s so hard for anything to get into the brain, how does waste get out?

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"However, the brain’s blood vessels are surrounded by open, fluid-filled spaces. In recent decades, the cerebrospinal fluid, or CSF, in those spaces has drawn a great deal of interest. “Maybe the CSF can be a highway, in a way, for the flow or exchange of different things within the brain,” said Steven Proulx, who studies the CSF system at the University of Bern.

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"A team at the University of Rochester led by the neurologist Maiken Nedergaard(opens a new tab) asked whether the slow pumping of the brain’s blood vessels might be able to push the fluid around, among, and in some cases through cells, to potentially drive a system of drainage. In a mouse model, researchers injected a glowing dye into CSF, manipulated the blood vessel walls to trigger a pumping action, and saw the dye concentration increase in the brain soon after. They concluded that the movement of blood vessels might be enough to move CSF, and possibly the brain’s waste, over long distances.

"The team took a further step in their interpretation. Because this kind of pumping — distinct from the familiar pulse from the heart — is regularly observed during sleep, they suggest that perhaps their observations can help explain why sleep feels refreshing. But it’s a hypothesis that not everyone agrees is well founded(opens a new tab). When it comes to ascribing purpose to the fluid moving through the brain, many researchers believe that the truth is still elusive.

"At the center of the brain are flooded caverns, like great cisterns shrouded in darkness, called ventricles. Cerebrospinal fluid seeps from the ventricle walls and then moves. Under pressure, it emerges elsewhere within the skull, flows down the neck and enters the spine.

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“Everyone accepts that there must be some kind of flow here,” said Christer Betsholtz(opens a new tab), a professor of vascular biology at the Karolinska Institute in Sweden. “About half a liter of CSF is produced in the ventricles every day, and it has to get out. People are still fighting about where the cerebrospinal fluid gets out.”

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"...Nedergaard, along with the neurologist Jeffrey Iliff(opens a new tab), then a postdoc in her lab, and their colleagues, injected a tracer into cerebrospinal fluid(opens a new tab) and watched it quickly arrive elsewhere. How did it get from one place to another? They proposed that the spaces around blood vessels commune with even smaller spaces deep in the brain, between individual cells. They also suggested that CSF moves through brain cells called astrocytes into those spaces. There, the fluid might drop off some molecules and pick up others; it may then wend its way back out to the spaces around blood vessels, and thence move waste out of the brain. All of this would have to be driven by a flow of uncertain mechanism.

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"In a 2013 paper, her team wrote that there was more movement of cerebrospinal fluid in sleeping and anesthetized mice than in waking ones — and that perhaps during sleep CSF sweeps waste out of the brain. Maybe this “brainwashing,” as headlines described it, could provide one reason why sleep is necessary, and explain how much better we feel after a good night of it.

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"In the years since those initial studies, a large number of papers(opens a new tab) referencing this brain-drainage theory, called the glymphatic hypothesis, have been published. It’s a catchy idea, but parts of the story raise red flags to some researchers who study the brain’s vasculature.

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"According to Betsholtz, there is no evidence that fluid is moving into the spaces around blood vessels that leave the brain.

"But many other researchers appear to have accepted the glymphatic hypothesis. That’s because it fills a hole in our understanding of the brain, said Donald McDonald(opens a new tab), who studies blood and lymph vessels at the UCSF School of Medicine. Personally, he doesn’t feel that the theory holds water, but he acknowledges its popularity. It fits comfortably in the space where there is a mystery.

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"For Nedergaard, Haugland and their collaborators, the findings tie together norepinephrine, the physical movement of blood vessels, and the flow of CSF in the brain. Nedergaard also asserts that the results are consistent with her group’s earlier finding that there is more brain drainage during sleep than during wakefulness.

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“'It’s clear that the brain has and needs a waste clearance system. … It’s really interesting to explore what that is and how that works.'”

Comment: the brain floats in a liquid which is a very good way to protect it from blows to the skull. The CSF must pick up waste and remove it. We still don't know how. Such a intricate system must be designed.