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  • Sleep. It's something we spend about a third of our lives doing,

  • but do any of us really understand what it's all about?

  • Two thousand years ago, Galen, one of the most prominent medical researchers of the ancient world,

  • proposed that while we're awake, our brain's motive force, its juice, would flow out to all the other parts of the body,

  • animating them but leaving the brain all dried up,

  • and he thought that when we sleep, all this moisture that filled the rest of the body would come rushing back,

  • rehydrating the brain and refreshing the mind. Now, that sounds completely ridiculous to us now,

  • but Galen was simply trying to explain something about sleep that we all deal with every day.

  • See, we all know based on our own experience that when you sleep, it clears your mind,

  • and when you don't sleep, it leaves your mind murky.

  • But while we know a great deal more about sleep now than when Galen was around,

  • we still haven't understood why it is that sleep, of all of our activities, has this incredible restorative function for the mind.

  • So today I want to tell you about some recent research that may shed new light on this question.

  • We've found that sleep may actually be a kind of elegant design solution to some of the brain's most basic needs,

  • a unique way that the brain meets the high demands and the narrow margins that set it apart from all the other organs of the body.

  • So almost all the biology that we observe can be thought of as a series of problems and their corresponding solutions,

  • and the first problem that every organ must solve is a continuous supply of nutrients to fuel all those cells of the body.

  • In the brain, that is especially critical;

  • its intense electrical activity uses up a quarter of the body's entire energy supply,

  • even though the brain accounts for only about two percent of the body's mass.

  • So the circulatory system solves the nutrient delivery problem by sending blood vessels

  • to supply nutrients and oxygen to every corner of our body.

  • You can actually see it in this video here. Here, we're imaging blood vessels in the brain of a living mouse.

  • The blood vessels form a complex network that fills the entire brain volume.

  • They start at the surface of the brain, and then they dive down into the tissue itself,

  • and as they spread out, they supply nutrients and oxygen to each and every cell in the brain.

  • Now, just as every cell requires nutrients to fuel it,

  • every cell also produces waste as a byproduct,

  • and the clearance of that waste is the second basic problem that each organ has to solve.

  • This diagram shows the body's lymphatic system, which has evolved to meet this need.

  • It's a second parallel network of vessels that extends throughout the body.

  • It takes up proteins and other waste from the spaces between the cells,

  • it collects them, and then dumps them into the blood so they can be disposed of.

  • But if you look really closely at this diagram, you'll see something that doesn't make a lot of sense.

  • So if we were to zoom into this guy's head, one of the things that you would see there is that there are no lymphatic vessels in the brain.

  • But that doesn't make a lot of sense, does it?

  • I mean, the brain is this intensely active organ that produces a correspondingly large amount of waste that must be efficiently cleared.

  • And yet, it lacks lymphatic vessels, which means that the approach that the rest of the body takes to clearing away its waste won't work in the brain.

  • So how, then, does the brain solve its waste clearance problem?

  • Well, that seemingly mundane question is where our group first jumped into this story,

  • and what we found as we dove down into the brain, down among the neurons and the blood vessels,

  • was that the brain's solution to the problem of waste clearance, it was really unexpected.

  • It was ingenious, but it was also beautiful. Let me tell you about what we found.

  • So the brain has this large pool of clean, clear fluid called cerebrospinal fluid.

  • We call it the CSF. The CSF fills the space that surrounds the brain,

  • and wastes from inside the brain make their way out to the CSF, which gets dumped, along with the waste, into the blood

  • So in that way, it sounds a lot like the lymphatic system, doesn't it?

  • But what's interesting is that the fluid and the waste from inside the brain,

  • they don't just percolate their way randomly out to these pools of CSF.

  • Instead, there is a specialized network of plumbing that organizes and facilitates this process.

  • You can see that in these videos. Here, we're again imaging into the brain of living mice.

  • The frame on your left shows what's happening at the brain's surface,

  • and the frame on your right shows what's happening down below the surface of the brain within the tissue itself.

  • We've labeled the blood vessels in red, and the CSF that's surrounding the brain will be in green.

  • Now, what was surprising to us was that the fluid on the outside of the brain, it didn't stay on the outside.

  • Instead, the CSF was pumped back into and through the brain along the outsides of the blood vessels,

  • and as it flushed down into the brain along the outsides of these vessels,

  • it was actually helping to clear away, to clean the waste from the spaces between the brain's cells.

  • If you think about it, using the outsides of these blood vessels like this is a really clever design solution,

  • because the brain is enclosed in a rigid skull and it's packed full of cells,

  • so there is no extra space inside it for a whole second set of vessels like the lymphatic system.

  • Yet the blood vessels, they extend from the surface of the brain down to reach every single cell in the brain,

  • which means that fluid that's traveling along the outsides of these vessels can gain easy access to the entire brain's volume,

  • so it's actually this really clever way to repurpose one set of vessels,

  • the blood vessels, to take over and replace the function of a second set of vessels, the lymphatic vessels, to make it so you don't need them.

  • And what's amazing is that no other organ takes quite this approach to clearing away the waste from between its cells.

  • This is a solution that is entirely unique to the brain.

  • But our most surprising finding was that all of this, everything I just told you about,

  • with all this fluid rushing through the brain, it's only happening in the sleeping brain.

  • Here, the video on the left shows how much of the CSF is moving through the brain of a living mouse while it's awake.

  • It's almost nothing. Yet in the same animal, if we wait just a little while until it's gone to sleep,

  • what we see is that the CSF is rushing through the brain, and we discovered that at the same time when the brain goes to sleep,

  • the brain cells themselves seem to shrink, opening up spaces in between them, allowing fluid to rush through and allowing waste to be cleared out.

  • So it seems that Galen may actually have been sort of on the right track

  • when he wrote about fluid rushing through the brain when sleep came on.

  • Our own research, now it's 2,000 years later, suggests that what's happening is that when the brain is awake and is at its most busy,

  • it puts off clearing away the waste from the spaces between its cells until later,

  • and then, when it goes to sleep and doesn't have to be as busy,

  • it shifts into a kind of cleaning mode to clear away the waste from the spaces between its brain,

  • the waste that's accumulated throughout the day.

  • So it's actually a little bit like how you or I,

  • we put off our household chores during the work week when we don't have time to get to it,

  • and then we play catch up on all the cleaning that we have to do when the weekend rolls around.

  • Now, I've just talked a lot about waste clearance,

  • but I haven't been very specific about the kinds of waste that the brain needs to be clearing during sleep in order to stay healthy.

  • The waste product that these recent studies focused most on is amyloid-beta, which is a protein that's made in the brain all the time.

  • My brain's making amyloid-beta right now, and so is yours.

  • But in patients with Alzheimer's disease, amyloid-beta builds up and aggregates in the spaces between the brain's cells,

  • instead of being cleared away like it's supposed to be,

  • and it's this buildup of amyloid-beta that's thought to be one of the key steps in the development of that terrible disease.

  • So we measured how fast amyloid-beta is cleared from the brain when it's awake versus when it's asleep,

  • and we found that indeed, the clearance of amyloid-beta is much more rapid from the sleeping brain.

  • So if sleep, then, is part of the brain's solution to the problem of waste clearance,

  • then this may dramatically change how we think about the relationship between sleep, amyloid-beta, and Alzheimer's disease.

  • A series of recent clinical studies suggest that among patients who haven't yet developed Alzheimer's disease,

  • worsening sleep quality and sleep duration are associated with a greater amount of amyloid-beta building up in the brain,

  • and while it's important to point out that these studies don't prove that lack of sleep or poor sleep cause Alzheimer's disease,

  • they do suggest that the failure of the brain to keep its house clean

  • by clearing away waste like amyloid-beta may contribute to the development of conditions like Alzheimer's.

  • So what this new research tells us, then, is that the one thing that all of you already knew about sleep,

  • that even Galen understood about sleep, that it refreshes and clears the mind,

  • may actually be a big part of what sleep is all about.

  • See, you and I, we go to sleep every single night, but our brains, they never rest.

  • While our body is still and our mind is off walking in dreams somewhere,

  • the elegant machinery of the brain is quietly hard at work cleaning and maintaining this unimaginably complex machine.

  • Like our housework, it's a dirty and a thankless job, but it's also important.

  • In your house, if you stop cleaning your kitchen for a month, your home will become completely unlivable very quickly.

  • But in the brain, the consequences of falling behind may be much greater than the embarrassment of dirty countertops,

  • because when it comes to cleaning the brain, it is the very health and function of the mind and the body that's at stake,

  • which is why understanding these very basic housekeeping functions of the brain today may be critical for preventing and treating diseases of the mind tomorrow.

  • Thank you.

Sleep. It's something we spend about a third of our lives doing,

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【TED】Jeff Iliff: One more reason to get a good night’s sleep

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