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TEDMED 2014

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

September 18, 2014

The brain uses a quarter of the body's entire energy supply, yet only accounts for about two percent of the body's mass. So how does this unique organ receive and, perhaps more importantly, rid itself of vital nutrients? New research suggests it has to do with sleep.

Jeff Iliff - Neuroscientist
Jeff Iliff is a neuroscientist who explores the unique functions of the brain. Full bio

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Double-click the English subtitles below to play the video.
Sleep.
00:12
It's something we spend about
a third of our lives doing,
00:14
but do any of us really understand what it's all about?
00:17
Two thousand years ago, Galen,
00:20
one of the most prominent medical researchers
00:22
of the ancient world,
00:25
proposed that while we're awake,
00:26
our brain's motive force, its juice,
00:28
would flow out to all the other parts of the body,
00:31
animating them but leaving the brain all dried up,
00:34
and he thought that when we sleep,
00:38
all this moisture that filled the rest of the body
00:40
would come rushing back,
00:42
rehydrating the brain
00:44
and refreshing the mind.
00:46
Now, that sounds completely ridiculous to us now,
00:48
but Galen was simply trying to explain
00:51
something about sleep
00:53
that we all deal with every day.
00:54
See, we all know based on our own experience
00:57
that when you sleep, it clears your mind,
00:59
and when you don't sleep,
01:02
it leaves your mind murky.
01:03
But while we know a great deal more about sleep now
01:06
than when Galen was around,
01:08
we still haven't understood why it is that sleep,
01:10
of all of our activities, has this incredible
01:13
restorative function for the mind.
01:16
So today I want to tell you about
01:18
some recent research
01:20
that may shed new light on this question.
01:21
We've found that sleep may actually be
01:24
a kind of elegant design solution
01:27
to some of the brain's most basic needs,
01:30
a unique way that the brain
01:32
meets the high demands and the narrow margins
01:34
that set it apart from all the other organs of the body.
01:37
So almost all the biology that we observe
01:42
can be thought of as a series of problems
01:45
and their corresponding solutions,
01:48
and the first problem that every organ must solve
01:50
is a continuous supply of nutrients to fuel
01:53
all those cells of the body.
01:56
In the brain, that is especially critical;
01:57
its intense electrical activity uses up
02:00
a quarter of the body's entire energy supply,
02:02
even though the brain accounts
02:05
for only about two percent of the body's mass.
02:07
So the circulatory system
02:10
solves the nutrient delivery problem
02:11
by sending blood vessels to supply nutrients
02:14
and oxygen to every corner of our body.
02:16
You can actually see it in this video here.
02:20
Here, we're imaging blood vessels
02:23
in the brain of a living mouse.
02:24
The blood vessels form a complex network
02:27
that fills the entire brain volume.
02:30
They start at the surface of the brain,
02:32
and then they dive down into the tissue itself,
02:34
and as they spread out, they supply nutrients
02:37
and oxygen to each and every cell in the brain.
02:39
Now, just as every cell requires
02:45
nutrients to fuel it,
02:48
every cell also produces waste as a byproduct,
02:50
and the clearance of that waste
02:53
is the second basic problem
02:55
that each organ has to solve.
02:57
This diagram shows the body's lymphatic system,
03:00
which has evolved to meet this need.
03:02
It's a second parallel network of vessels
03:05
that extends throughout the body.
03:07
It takes up proteins and other waste
03:09
from the spaces between the cells,
03:11
it collects them, and then dumps them into the blood
03:13
so they can be disposed of.
03:16
But if you look really closely at this diagram,
03:18
you'll see something
03:20
that doesn't make a lot of sense.
03:22
So if we were to zoom into this guy's head,
03:24
one of the things that you would see there
03:27
is that there are no lymphatic vessels in the brain.
03:29
But that doesn't make a lot of sense, does it?
03:33
I mean, the brain is this intensely active organ
03:36
that produces a correspondingly
large amount of waste
03:39
that must be efficiently cleared.
03:42
And yet, it lacks lymphatic vessels, which means that
03:44
the approach that the rest of the body takes
03:47
to clearing away its waste
03:49
won't work in the brain.
03:51
So how, then, does the brain solve
03:54
its waste clearance problem?
03:56
Well, that seemingly mundane question
03:58
is where our group first jumped into this story,
04:02
and what we found
04:05
as we dove down into the brain,
04:07
down among the neurons and the blood vessels,
04:09
was that the brain's solution
04:12
to the problem of waste clearance,
04:15
it was really unexpected.
04:17
It was ingenious,
04:19
but it was also beautiful.
04:22
Let me tell you about what we found.
04:25
So the brain has this large pool
04:27
of clean, clear fluid called cerebrospinal fluid.
04:29
We call it the CSF.
04:33
The CSF fills the space that surrounds the brain,
04:34
and wastes from inside the brain
04:38
make their way out to the CSF,
04:39
which gets dumped, along with
the waste, into the blood.
04:42
So in that way, it sounds a lot like
04:45
the lymphatic system, doesn't it?
04:46
But what's interesting is that the fluid and the waste
04:49
from inside the brain,
04:51
they don't just percolate their way randomly
04:53
out to these pools of CSF.
04:55
Instead, there is a specialized network of plumbing
04:58
that organizes and facilitates this process.
05:02
You can see that in these videos.
05:05
Here, we're again imaging into the brain
05:08
of living mice.
05:11
The frame on your left shows
05:12
what's happening at the brain's surface,
05:14
and the frame on your right shows
05:16
what's happening down below the surface of the brain
05:18
within the tissue itself.
05:20
We've labeled the blood vessels in red,
05:21
and the CSF that's surrounding the brain
05:24
will be in green.
05:26
Now, what was surprising to us
05:27
was that the fluid on the outside of the brain,
05:29
it didn't stay on the outside.
05:32
Instead, the CSF was pumped back into
05:35
and through the brain
05:39
along the outsides of the blood vessels,
05:41
and as it flushed down into the brain
05:44
along the outsides of these vessels,
05:46
it was actually helping to clear away,
05:48
to clean the waste from the spaces
05:51
between the brain's cells.
05:53
If you think about it,
05:56
using the outsides of these blood vessels like this
05:58
is a really clever design solution,
06:01
because the brain is enclosed
06:04
in a rigid skull
06:07
and it's packed full of cells,
06:08
so there is no extra space inside it
06:10
for a whole second set of vessels
like the lymphatic system.
06:13
Yet the blood vessels,
06:17
they extend from the surface of the brain
06:18
down to reach every single cell in the brain,
06:20
which means that fluid
06:23
that's traveling along the outsides of these vessels
06:24
can gain easy access to the entire brain's volume,
06:27
so it's actually this really clever way
06:31
to repurpose one set of vessels, the blood vessels,
06:33
to take over and replace the function
06:37
of a second set of vessels, the lymphatic vessels,
06:40
to make it so you don't need them.
06:43
And what's amazing is that no other organ
06:45
takes quite this approach
06:48
to clearing away the waste from between its cells.
06:49
This is a solution that is entirely unique to the brain.
06:52
But our most surprising finding
06:58
was that all of this,
07:00
everything I just told you about,
07:03
with all this fluid rushing through the brain,
07:05
it's only happening in the sleeping brain.
07:08
Here, the video on the left
07:12
shows how much of the CSF is moving
07:14
through the brain of a living mouse while it's awake.
07:16
It's almost nothing.
07:20
Yet in the same animal,
07:22
if we wait just a little while until it's gone to sleep,
07:23
what we see is that the CSF
07:26
is rushing through the brain,
07:29
and we discovered that at the same time
07:31
when the brain goes to sleep,
07:34
the brain cells themselves seem to shrink,
07:36
opening up spaces in between them,
07:39
allowing fluid to rush through
07:41
and allowing waste to be cleared out.
07:43
So it seems that Galen may actually have been
07:46
sort of on the right track when he wrote about
07:48
fluid rushing through the brain
07:51
when sleep came on.
07:53
Our own research, now it's 2,000 years later,
07:55
suggests that what's happening is that
07:58
when the brain is awake
08:00
and is at its most busy,
08:03
it puts off clearing away the waste
08:05
from the spaces between its cells until later,
08:07
and then, when it goes to sleep
08:10
and doesn't have to be as busy,
08:12
it shifts into a kind of cleaning mode
08:14
to clear away the waste
08:17
from the spaces between its cells,
08:19
the waste that's accumulated throughout the day.
08:20
So it's actually a little bit like how you or I,
08:22
we put off our household chores during the work week
08:25
when we don't have time to get to it,
08:28
and then we play catch up on all
the cleaning that we have to do
08:29
when the weekend rolls around.
08:33
Now, I've just talked a lot about waste clearance,
08:35
but I haven't been very specific
08:39
about the kinds of waste
08:40
that the brain needs to be clearing
08:42
during sleep in order to stay healthy.
08:44
The waste product that these recent studies
08:46
focused most on is amyloid-beta,
08:48
which is a protein that's made
in the brain all the time.
08:50
My brain's making amyloid-beta right now,
08:54
and so is yours.
08:55
But in patients with Alzheimer's disease,
08:58
amyloid-beta builds up and aggregates
09:00
in the spaces between the brain's cells,
09:02
instead of being cleared away
like it's supposed to be,
09:04
and it's this buildup of amyloid-beta
09:08
that's thought to be one of the key steps
09:10
in the development of that terrible disease.
09:12
So we measured how fast amyloid-beta is cleared
09:15
from the brain when it's awake
09:18
versus when it's asleep,
09:19
and we found that indeed,
09:21
the clearance of amyloid-beta
09:23
is much more rapid from the sleeping brain.
09:25
So if sleep, then,
09:29
is part of the brain's solution
09:31
to the problem of waste clearance,
09:33
then this may dramatically change how we think
09:35
about the relationship between sleep,
09:37
amyloid-beta, and Alzheimer's disease.
09:40
A series of recent clinical studies
09:43
suggest that among patients
09:45
who haven't yet developed Alzheimer's disease,
09:47
worsening sleep quality and sleep duration
09:50
are associated with a greater amount
09:53
of amyloid-beta building up in the brain,
09:55
and while it's important to point out
09:58
that these studies don't prove
10:00
that lack of sleep or poor sleep
10:01
cause Alzheimer's disease,
10:04
they do suggest that the failure of the brain
10:06
to keep its house clean
10:09
by clearing away waste like amyloid-beta
10:10
may contribute to the development
10:13
of conditions like Alzheimer's.
10:15
So what this new research tells us, then,
10:19
is that the one thing that all of you
10:21
already knew about sleep,
10:23
that even Galen understood about sleep,
10:24
that it refreshes and clears the mind,
10:27
may actually be a big part
10:30
of what sleep is all about.
10:32
See, you and I, we go to sleep
10:34
every single night,
10:36
but our brains, they never rest.
10:37
While our body is still
10:40
and our mind is off walking in dreams somewhere,
10:42
the elegant machinery of the brain
10:45
is quietly hard at work
10:47
cleaning and maintaining
10:49
this unimaginably complex machine.
10:51
Like our housework,
10:54
it's a dirty and a thankless job,
10:55
but it's also important.
10:58
In your house, if you stop cleaning your kitchen
11:00
for a month,
11:02
your home will become completely unlivable
11:04
very quickly.
11:07
But in the brain, the consequences
11:08
of falling behind may be much greater
11:10
than the embarrassment of dirty countertops,
11:13
because when it comes to cleaning the brain,
11:16
it is the very health and function
11:19
of the mind and the body that's at stake,
11:21
which is why understanding these
11:24
very basic housekeeping functions of the brain today
11:26
may be critical for preventing and treating
11:30
diseases of the mind tomorrow.
11:33
Thank you.
11:36
(Applause)
11:38

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Jeff Iliff - Neuroscientist
Jeff Iliff is a neuroscientist who explores the unique functions of the brain.

Why you should listen
Neuroscientist Jeff Iliff 's research follows two main paths. The first is the exploration of how the brain’s support cells, called glia, contribute to maintaining the proper environment for neuronal function and how their failure in conditions like vascular dementia, stroke, and traumatic brain injury leads to neurodegeneration. The second seeks to define the basic cellular mechanisms by which brain blood flow is coordinated up and down the vascular tree. Now an Assistant Professor of Anesthesiology and Perioperative Medicine at Oregon Health & Science University, Jeff was a part of a University of Rochester Medical Center team that discovered a brain cleansing system, which they dubbed the “glymphatic system.”
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