ABOUT THE SPEAKER
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.”
More profile about the speaker
Jeff Iliff | Speaker | TED.com
TEDMED 2014

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

Filmed:
5,135,628 views

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

Double-click the English transcript below to play the video.

00:12
Sleep.
0
741
1642
00:14
It's something we spend about
a third of our lives doing,
1
2383
2821
00:17
but do any of us really understand what it's all about?
2
5204
3321
00:20
Two thousand years ago, Galen,
3
8525
2215
00:22
one of the most prominent medical researchers
4
10740
2140
00:25
of the ancient world,
5
12880
1059
00:26
proposed that while we're awake,
6
13939
2319
00:28
our brain's motive force, its juice,
7
16258
3362
00:31
would flow out to all the other parts of the body,
8
19620
2570
00:34
animating them but leaving the brain all dried up,
9
22190
4014
00:38
and he thought that when we sleep,
10
26204
1616
00:40
all this moisture that filled the rest of the body
11
27820
2538
00:42
would come rushing back,
12
30358
1744
00:44
rehydrating the brain
13
32102
1811
00:46
and refreshing the mind.
14
33913
2546
00:48
Now, that sounds completely ridiculous to us now,
15
36459
2421
00:51
but Galen was simply trying to explain
16
38880
2041
00:53
something about sleep
17
40921
1607
00:54
that we all deal with every day.
18
42528
2657
00:57
See, we all know based on our own experience
19
45185
1924
00:59
that when you sleep, it clears your mind,
20
47109
2712
01:02
and when you don't sleep,
21
49821
1462
01:03
it leaves your mind murky.
22
51283
2927
01:06
But while we know a great deal more about sleep now
23
54210
2512
01:08
than when Galen was around,
24
56722
1804
01:10
we still haven't understood why it is that sleep,
25
58526
2880
01:13
of all of our activities, has this incredible
26
61406
2629
01:16
restorative function for the mind.
27
64035
2719
01:18
So today I want to tell you about
28
66754
1500
01:20
some recent research
29
68254
1356
01:21
that may shed new light on this question.
30
69610
2758
01:24
We've found that sleep may actually be
31
72368
3205
01:27
a kind of elegant design solution
32
75573
2373
01:30
to some of the brain's most basic needs,
33
77946
2577
01:32
a unique way that the brain
34
80523
1946
01:34
meets the high demands and the narrow margins
35
82469
2823
01:37
that set it apart from all the other organs of the body.
36
85292
4999
01:42
So almost all the biology that we observe
37
90291
3055
01:45
can be thought of as a series of problems
38
93346
2454
01:48
and their corresponding solutions,
39
95800
2041
01:50
and the first problem that every organ must solve
40
97841
3480
01:53
is a continuous supply of nutrients to fuel
41
101321
2498
01:56
all those cells of the body.
42
103819
1741
01:57
In the brain, that is especially critical;
43
105560
2578
02:00
its intense electrical activity uses up
44
108138
2217
02:02
a quarter of the body's entire energy supply,
45
110355
2858
02:05
even though the brain accounts
46
113213
1630
02:07
for only about two percent of the body's mass.
47
114843
3337
02:10
So the circulatory system
48
118180
1612
02:11
solves the nutrient delivery problem
49
119792
2431
02:14
by sending blood vessels to supply nutrients
50
122223
2540
02:16
and oxygen to every corner of our body.
51
124763
3343
02:20
You can actually see it in this video here.
52
128106
3014
02:23
Here, we're imaging blood vessels
53
131120
1582
02:24
in the brain of a living mouse.
54
132702
2895
02:27
The blood vessels form a complex network
55
135597
2520
02:30
that fills the entire brain volume.
56
138117
2348
02:32
They start at the surface of the brain,
57
140465
1801
02:34
and then they dive down into the tissue itself,
58
142266
2881
02:37
and as they spread out, they supply nutrients
59
145147
2361
02:39
and oxygen to each and every cell in the brain.
60
147508
5765
02:45
Now, just as every cell requires
61
153276
2970
02:48
nutrients to fuel it,
62
156246
1891
02:50
every cell also produces waste as a byproduct,
63
158137
3140
02:53
and the clearance of that waste
64
161277
1546
02:55
is the second basic problem
65
162823
2267
02:57
that each organ has to solve.
66
165090
2792
03:00
This diagram shows the body's lymphatic system,
67
167882
2583
03:02
which has evolved to meet this need.
68
170465
2430
03:05
It's a second parallel network of vessels
69
172895
2812
03:07
that extends throughout the body.
70
175707
2014
03:09
It takes up proteins and other waste
71
177721
1957
03:11
from the spaces between the cells,
72
179678
1924
03:13
it collects them, and then dumps them into the blood
73
181602
2812
03:16
so they can be disposed of.
74
184414
2261
03:18
But if you look really closely at this diagram,
75
186675
1789
03:20
you'll see something
76
188464
1394
03:22
that doesn't make a lot of sense.
77
189858
2328
03:24
So if we were to zoom into this guy's head,
78
192186
2757
03:27
one of the things that you would see there
79
194943
2193
03:29
is that there are no lymphatic vessels in the brain.
80
197136
4162
03:33
But that doesn't make a lot of sense, does it?
81
201298
3094
03:36
I mean, the brain is this intensely active organ
82
204392
3205
03:39
that produces a correspondingly
large amount of waste
83
207597
2565
03:42
that must be efficiently cleared.
84
210162
2577
03:44
And yet, it lacks lymphatic vessels, which means that
85
212739
2962
03:47
the approach that the rest of the body takes
86
215701
1796
03:49
to clearing away its waste
87
217497
1985
03:51
won't work in the brain.
88
219482
3009
03:54
So how, then, does the brain solve
89
222491
2048
03:56
its waste clearance problem?
90
224539
1754
03:58
Well, that seemingly mundane question
91
226293
3689
04:02
is where our group first jumped into this story,
92
229982
3408
04:05
and what we found
93
233390
2021
04:07
as we dove down into the brain,
94
235411
2335
04:09
down among the neurons and the blood vessels,
95
237746
2891
04:12
was that the brain's solution
96
240637
2183
04:15
to the problem of waste clearance,
97
242820
2563
04:17
it was really unexpected.
98
245383
1817
04:19
It was ingenious,
99
247200
2850
04:22
but it was also beautiful.
100
250050
3118
04:25
Let me tell you about what we found.
101
253168
1667
04:27
So the brain has this large pool
102
254835
2554
04:29
of clean, clear fluid called cerebrospinal fluid.
103
257389
3461
04:33
We call it the CSF.
104
260850
1319
04:34
The CSF fills the space that surrounds the brain,
105
262169
3980
04:38
and wastes from inside the brain
106
266149
1523
04:39
make their way out to the CSF,
107
267672
2222
04:42
which gets dumped, along with
the waste, into the blood.
108
269894
3263
04:45
So in that way, it sounds a lot like
109
273157
1120
04:46
the lymphatic system, doesn't it?
110
274277
2592
04:49
But what's interesting is that the fluid and the waste
111
276869
2756
04:51
from inside the brain,
112
279625
1732
04:53
they don't just percolate their way randomly
113
281357
2407
04:55
out to these pools of CSF.
114
283764
2374
04:58
Instead, there is a specialized network of plumbing
115
286138
3723
05:02
that organizes and facilitates this process.
116
289861
3892
05:05
You can see that in these videos.
117
293753
2149
05:08
Here, we're again imaging into the brain
118
295902
3038
05:11
of living mice.
119
298940
1484
05:12
The frame on your left shows
120
300424
1923
05:14
what's happening at the brain's surface,
121
302347
2059
05:16
and the frame on your right shows
122
304406
1564
05:18
what's happening down below the surface of the brain
123
305970
1946
05:20
within the tissue itself.
124
307916
1723
05:21
We've labeled the blood vessels in red,
125
309639
2259
05:24
and the CSF that's surrounding the brain
126
311898
2024
05:26
will be in green.
127
313922
1823
05:27
Now, what was surprising to us
128
315745
1800
05:29
was that the fluid on the outside of the brain,
129
317545
3251
05:32
it didn't stay on the outside.
130
320796
2812
05:35
Instead, the CSF was pumped back into
131
323608
3403
05:39
and through the brain
132
327011
1873
05:41
along the outsides of the blood vessels,
133
328884
3032
05:44
and as it flushed down into the brain
134
331916
2384
05:46
along the outsides of these vessels,
135
334300
1800
05:48
it was actually helping to clear away,
136
336100
2812
05:51
to clean the waste from the spaces
137
338912
2441
05:53
between the brain's cells.
138
341353
2846
05:56
If you think about it,
139
344199
1912
05:58
using the outsides of these blood vessels like this
140
346111
3477
06:01
is a really clever design solution,
141
349588
2519
06:04
because the brain is enclosed
142
352107
2722
06:07
in a rigid skull
143
354829
1823
06:08
and it's packed full of cells,
144
356652
2103
06:10
so there is no extra space inside it
145
358755
2745
06:13
for a whole second set of vessels
like the lymphatic system.
146
361500
3600
06:17
Yet the blood vessels,
147
365100
1259
06:18
they extend from the surface of the brain
148
366359
1958
06:20
down to reach every single cell in the brain,
149
368317
2609
06:23
which means that fluid
150
370926
1238
06:24
that's traveling along the outsides of these vessels
151
372164
3296
06:27
can gain easy access to the entire brain's volume,
152
375460
3800
06:31
so it's actually this really clever way
153
379260
2184
06:33
to repurpose one set of vessels, the blood vessels,
154
381444
3765
06:37
to take over and replace the function
155
385209
2789
06:40
of a second set of vessels, the lymphatic vessels,
156
387998
3183
06:43
to make it so you don't need them.
157
391181
2411
06:45
And what's amazing is that no other organ
158
393592
2317
06:48
takes quite this approach
159
395909
1641
06:49
to clearing away the waste from between its cells.
160
397550
3060
06:52
This is a solution that is entirely unique to the brain.
161
400610
5820
06:58
But our most surprising finding
162
406430
2268
07:00
was that all of this,
163
408698
2103
07:03
everything I just told you about,
164
410801
2350
07:05
with all this fluid rushing through the brain,
165
413151
3318
07:08
it's only happening in the sleeping brain.
166
416469
4184
07:12
Here, the video on the left
167
420653
1450
07:14
shows how much of the CSF is moving
168
422103
2261
07:16
through the brain of a living mouse while it's awake.
169
424364
3606
07:20
It's almost nothing.
170
427970
1873
07:22
Yet in the same animal,
171
429843
1575
07:23
if we wait just a little while until it's gone to sleep,
172
431418
3205
07:26
what we see is that the CSF
173
434623
2757
07:29
is rushing through the brain,
174
437380
2418
07:31
and we discovered that at the same time
175
439798
2160
07:34
when the brain goes to sleep,
176
441958
2612
07:36
the brain cells themselves seem to shrink,
177
444570
2663
07:39
opening up spaces in between them,
178
447233
2037
07:41
allowing fluid to rush through
179
449270
2137
07:43
and allowing waste to be cleared out.
180
451407
2733
07:46
So it seems that Galen may actually have been
181
454140
2514
07:48
sort of on the right track when he wrote about
182
456654
2256
07:51
fluid rushing through the brain
183
458910
2700
07:53
when sleep came on.
184
461610
1642
07:55
Our own research, now it's 2,000 years later,
185
463252
3453
07:58
suggests that what's happening is that
186
466705
2070
08:00
when the brain is awake
187
468775
2059
08:03
and is at its most busy,
188
470834
2114
08:05
it puts off clearing away the waste
189
472948
2362
08:07
from the spaces between its cells until later,
190
475310
3071
08:10
and then, when it goes to sleep
191
478381
1859
08:12
and doesn't have to be as busy,
192
480240
2348
08:14
it shifts into a kind of cleaning mode
193
482588
2577
08:17
to clear away the waste
194
485165
1687
08:19
from the spaces between its cells,
195
486852
1508
08:20
the waste that's accumulated throughout the day.
196
488360
2417
08:22
So it's actually a little bit like how you or I,
197
490777
2408
08:25
we put off our household chores during the work week
198
493185
3082
08:28
when we don't have time to get to it,
199
496267
1462
08:29
and then we play catch up on all
the cleaning that we have to do
200
497729
3261
08:33
when the weekend rolls around.
201
500990
2758
08:35
Now, I've just talked a lot about waste clearance,
202
503748
3272
08:39
but I haven't been very specific
203
507020
1452
08:40
about the kinds of waste
204
508472
1394
08:42
that the brain needs to be clearing
205
509866
2295
08:44
during sleep in order to stay healthy.
206
512161
2543
08:46
The waste product that these recent studies
207
514704
1597
08:48
focused most on is amyloid-beta,
208
516301
2418
08:50
which is a protein that's made
in the brain all the time.
209
518719
3195
08:54
My brain's making amyloid-beta right now,
210
521914
1858
08:55
and so is yours.
211
523772
2158
08:58
But in patients with Alzheimer's disease,
212
525930
2002
09:00
amyloid-beta builds up and aggregates
213
527932
2599
09:02
in the spaces between the brain's cells,
214
530531
2013
09:04
instead of being cleared away
like it's supposed to be,
215
532544
3426
09:08
and it's this buildup of amyloid-beta
216
535970
2010
09:10
that's thought to be one of the key steps
217
537980
2213
09:12
in the development of that terrible disease.
218
540193
2621
09:15
So we measured how fast amyloid-beta is cleared
219
542814
3094
09:18
from the brain when it's awake
220
545908
1732
09:19
versus when it's asleep,
221
547640
1778
09:21
and we found that indeed,
222
549418
1878
09:23
the clearance of amyloid-beta
223
551296
1890
09:25
is much more rapid from the sleeping brain.
224
553186
4519
09:29
So if sleep, then,
225
557705
1679
09:31
is part of the brain's solution
226
559384
1958
09:33
to the problem of waste clearance,
227
561342
2010
09:35
then this may dramatically change how we think
228
563352
2376
09:37
about the relationship between sleep,
229
565728
2235
09:40
amyloid-beta, and Alzheimer's disease.
230
567963
3356
09:43
A series of recent clinical studies
231
571319
1958
09:45
suggest that among patients
232
573277
1833
09:47
who haven't yet developed Alzheimer's disease,
233
575110
3094
09:50
worsening sleep quality and sleep duration
234
578204
3066
09:53
are associated with a greater amount
235
581270
2018
09:55
of amyloid-beta building up in the brain,
236
583288
2812
09:58
and while it's important to point out
237
586100
1867
10:00
that these studies don't prove
238
587967
1710
10:01
that lack of sleep or poor sleep
239
589677
2189
10:04
cause Alzheimer's disease,
240
591866
2407
10:06
they do suggest that the failure of the brain
241
594273
2610
10:09
to keep its house clean
242
596883
1912
10:10
by clearing away waste like amyloid-beta
243
598795
2756
10:13
may contribute to the development
244
601551
1902
10:15
of conditions like Alzheimer's.
245
603453
3617
10:19
So what this new research tells us, then,
246
607070
1905
10:21
is that the one thing that all of you
247
608975
2327
10:23
already knew about sleep,
248
611302
1408
10:24
that even Galen understood about sleep,
249
612710
2653
10:27
that it refreshes and clears the mind,
250
615363
3071
10:30
may actually be a big part
251
618434
1541
10:32
of what sleep is all about.
252
619975
2317
10:34
See, you and I, we go to sleep
253
622292
1518
10:36
every single night,
254
623810
1733
10:37
but our brains, they never rest.
255
625543
3003
10:40
While our body is still
256
628546
1834
10:42
and our mind is off walking in dreams somewhere,
257
630380
3071
10:45
the elegant machinery of the brain
258
633451
1676
10:47
is quietly hard at work
259
635127
1980
10:49
cleaning and maintaining
260
637107
2193
10:51
this unimaginably complex machine.
261
639300
2835
10:54
Like our housework,
262
642135
1041
10:55
it's a dirty and a thankless job,
263
643176
2749
10:58
but it's also important.
264
645925
2255
11:00
In your house, if you stop cleaning your kitchen
265
648180
2403
11:02
for a month,
266
650583
1908
11:04
your home will become completely unlivable
267
652491
2439
11:07
very quickly.
268
654930
1607
11:08
But in the brain, the consequences
269
656537
2088
11:10
of falling behind may be much greater
270
658625
2931
11:13
than the embarrassment of dirty countertops,
271
661556
2728
11:16
because when it comes to cleaning the brain,
272
664284
2564
11:19
it is the very health and function
273
666848
2376
11:21
of the mind and the body that's at stake,
274
669224
2945
11:24
which is why understanding these
275
672169
2241
11:26
very basic housekeeping functions of the brain today
276
674410
4272
11:30
may be critical for preventing and treating
277
678682
2993
11:33
diseases of the mind tomorrow.
278
681675
3028
11:36
Thank you.
279
684703
2048
11:38
(Applause)
280
686751
1767

▲Back to top

ABOUT THE SPEAKER
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.”
More profile about the speaker
Jeff Iliff | Speaker | TED.com