The brain may be able to repair itself -- with help | Jocelyne Bloch

翻译人员: Yolanda Zhang 校对人员: Yinchun Rui

So I'm a neurosurgeon.

我是一名神经外科医生。

And like most of my colleagues,

跟我的大多数同事一样，

I have to deal, every day, with human tragedies.

我每天都要面对各种人世间的悲剧。

I realize how your life can change from one second to the other

我认识到一次严重的中风 或者一次车祸，

after a major stroke or after a car accident.

就足以在下一秒改变一个人的命运。

And what is very frustrating for us neurosurgeons

对我们这些神经外科医生来说， 最难过的事情就是意识到

is to realize that unlike other organs of the body,

与其他身体器官不同，

the brain has very little ability for self-repair.

大脑几乎不能进行自我修复。

And after a major injury of your central nervous system,

在中枢神经系统受到一次严重损伤后，

the patients often remain with a severe handicap.

患者将会终身面对严重的残疾。

And that's probably the reason why I've chosen

这可能也是我想要成为一名

to be a functional neurosurgeon.

功能性神经外科医生的原因。

What is a functional neurosurgeon?

功能性神经外科医生是做什么的？

It's a doctor who is trying to improve a neurological function

他们主要通过各种不同的手术方法

through different surgical strategies.

来改善神经功能。

You've certainly heard of one of the famous ones

你们一定听说过 很多主流方法中的一个，

called deep brain stimulation,

叫做深度脑电刺激，

where you implant an electrode in the depths of the brain

通常是把一个电极植入大脑深处，

in order to modulate a circuit of neurons

通过调控神经元电流

to improve a neurological function.

来改善神经功能。

It's really an amazing technology

这项技术不可思议地

in that it has improved the destiny of patients

扭转了患有帕金森，

with Parkinson's disease,

和被颤抖及疼痛困扰的

with severe tremor, with severe pain.

患者的命运。

However, neuromodulation does not mean neuro-repair.

但是，神经调控并不意味着 神经元的修复。

And the dream of functional neurosurgeons

而功能性神经外科医生希望有朝一日

is to repair the brain.

能够修复受损的大脑。

I think

我认为

that we are approaching this dream.

我们正在一步步接近这个目标。

And I would like to show you

我想让大家看看

that we are very close to this.

我们离成功已经近在咫尺了。

And that with a little bit of help,

只需要一点点的人工辅助，

the brain is able to help itself.

大脑就可以进行自我修复。

So the story started 15 years ago.

事情还要从15年前说起。

At that time, I was a chief resident

那时候我还是一名住院总医师，

working days and nights in the emergency room.

夜以继日地在急诊室忙碌。

I often had to take care of patients with head trauma.

我经常要护理有大脑损伤的病患。

You have to imagine that when a patient comes in with a severe head trauma,

你们可以想象一下， 带有严重脑外伤的患者被推进来，

his brain is swelling

他的大脑不断肿胀，

颅内压越来越高。

and he's increasing his intracranial pressure.

And in order to save his life,

要挽救他的生命，

you have to decrease this intracranial pressure.

就必须要降低颅内压。

And to do that,

要做到这一点，

you sometimes have to remove a piece of swollen brain.

有时候就需要移除一部分肿胀的脑组织。

So instead of throwing away these pieces of swollen brain,

不过我们并没有把这一部分 肿胀的大脑直接丢弃，

we decided with Jean-François Brunet,

而是在与生物学家 ， 也是我的一位同事

who is a colleague of mine, a biologist,

Jean-François Brunet商量之后，

to study them.

决定对这部分组织进行进一步研究。

What do I mean by that?

具体要怎么研究呢？

We wanted to grow cells from these pieces of tissue.

我们想让这一部分组织长出细胞来。

It's not an easy task.

这可不是件容易的事儿。

Growing cells from a piece of tissue

让组织生长出细胞，

is a bit the same as growing very small children

就好比一个家庭开始

out from their family.

养育一个小宝宝。

So you need to find the right nutrients,

需要找到合适的营养成分，

合适的温度和湿度，

the warmth, the humidity

and all the nice environments to make them thrive.

保证它们能够在适宜的环境下存活。

So that's exactly what we had to do with these cells.

我们就是要在这样的条件下 培养这些细胞。

And after many attempts,

尝试过很多次之后，

Jean-François did it.

Jean-François成功了。

And that's what he saw under his microscope.

这就是他在显微镜下看到的一幕。

And that was, for us, a major surprise.

对我们来说，这是个天大的惊喜。

Why?

为什么呢？

Because this looks exactly the same as a stem cell culture,

因为这看起来跟干细胞群落 几乎一模一样，

with large green cells surrounding small, immature cells.

小的，尚未成熟的细胞被一大群 绿色，较大的细胞包围着。

And you may remember from biology class

你们可能还记得生物课上讲过，

that stem cells are immature cells,

干细胞是未发育成熟的细胞，

able to turn into any type of cell of the body.

可以演变成人体的任何一种细胞。

The adult brain has stem cells, but they're very rare

成人的大脑也有干细胞， 但是数量很少，

and they're located in deep and small niches

而且分布于大脑深处

in the depths of the brain.

隐蔽的角落里。

So it was surprising to get this kind of stem cell culture

所以能够在操作室里从肿胀的

from the superficial part of swollen brain we had

大脑表面获得这种干细胞群落，

in the operating theater.

真是太让人意外了。

And there was another intriguing observation:

而我们还观察到了 另外一个有趣的现象：

Regular stem cells are very active cells --

正常的干细胞非常活跃——

cells that divide, divide, divide very quickly.

它们可以不断地进行快速分裂。

And they never die, they're immortal cells.

它们也不会凋亡，能够一直存活。

But these cells behave differently.

但是这些细胞却有着不同的行为。

They divide slowly,

它们分裂得很慢，

and after a few weeks of culture,

而且仅仅过了几个星期，

they even died.

就会慢慢死掉。

So we were in front of a strange new cell population

于是我们面前就出现了 一个奇怪的新的细胞群落，

that looked like stem cells but behaved differently.

看起来像干细胞， 但其行为却又跟干细胞有着天壤之别。

And it took us a long time to understand where they came from.

我们花了好长时间 才搞清楚它们是从哪儿来的。

They come from these cells.

它们来自于这些细胞。

These blue and red cells are called doublecortin-positive cells.

这些蓝色和红色的细胞称为 DCX（doublecortin-positive）阳性细胞。

All of you have them in your brain.

它们存在于我们每个人的大脑中，

They represent four percent of your cortical brain cells.

组成了我们4%的大脑皮层细胞。

They have a very important role during the development stage.

在大脑发育过程中， 这些细胞起着至关重要的作用。

When you were fetuses,

在婴儿时期，

they helped your brain to fold itself.

它们能帮助大脑产生褶皱。

But why do they stay in your head?

但它们为什么会一直留在大脑中呢？

This, we don't know.

这一点我们还不清楚。

We think that they may participate in brain repair

我们认为它们可能参与了大脑修复，

because we find them in higher concentration

是因为我们发现在大脑损伤的部位

close to brain lesions.

它们的浓度比较高。

But it's not so sure.

但我们还不是非常确定。

But there is one clear thing --

但有一点已经很清楚了——

that from these cells,

也就是从这些细胞中，

we got our stem cell culture.

我们得到了干细胞群落。

And we were in front of a potential new source of cells

我们面前正是一群有可能修复大脑的

细胞的新来源。

to repair the brain.

And we had to prove this.

我们需要证明这一点。

So to prove it,

那么想要证明，

we decided to design an experimental paradigm.

我们决定设计一组对照试实验。

The idea was to biopsy a piece of brain

基本概念就是在大脑中一块

in a non-eloquent area of the brain,

功能尚不明确的区域进行活组织提取，

and then to culture the cells

然后用Jean-François在实验室

exactly the way Jean-François did it in his lab.

尝试过的同样的方法培养细胞。

And then label them, to put color in them

然后给它们做标记，染色，

in order to be able to track them in the brain.

这样就可以在大脑中追踪它们的活动。

And the last step was to re-implant them

最后一步就是把它们重新移植入

in the same individual.

相同的个体中。

We call these

我们把这叫做

autologous grafts -- autografts.

自体同源嫁接——自嫁接。

So the first question we had,

我们的第一个问题就是，

"What will happen if we re-implant these cells in a normal brain,

“如果我们把这些细胞 重新植入一个正常的大脑，

and what will happen if we re-implant the same cells

或者一个受过损伤的大脑，

in a lesioned brain?"

会有什么区别呢？”

Thanks to the help of professor Eric Rouiller,

很幸运，在Eric Rouiller教授的帮助下，

we worked with monkeys.

我们得以在猴子身上进行试验。

So in the first-case scenario,

在第一种情况中，

we re-implanted the cells in the normal brain

我们把这些细胞移植入了正常大脑中，

and what we saw is that they completely disappeared after a few weeks,

发现它们在 仅仅几周后就完全消失了，

as if they were taken from the brain,

就好像被从大脑中清除了一样，

they go back home,

它们被驱赶出了这一区域，

the space is already busy,

这里没有多余的空间了，

they are not needed there, so they disappear.

它们发挥不了任何作用，于是就消失了。

In the second-case scenario,

在第二种情况中，

we performed the lesion,

我们用了受损的大脑，

把一模一样的细胞移植了进去，

we re-implanted exactly the same cells,

and in this case, the cells remained --

而这一次，细胞存活了下来——

and they became mature neurons.

它们发育成了成熟的神经细胞。

And that's the image of what we could observe under the microscope.

这就是我们在显微镜下看到的图像。

Those are the cells that were re-implanted.

这些是重新移植过的细胞。

And the proof they carry,

证据表明，

these little spots, those are the cells that we've labeled

这些小点就是我们在体外标记过的

还处在群落状态下的细胞。

in vitro, when they were in culture.

But we could not stop here, of course.

但这肯定还远远不够。

Do these cells also help a monkey to recover after a lesion?

那么这些细胞到底会不会 修复猴子的脑损伤呢？

So for that, we trained monkeys to perform a manual dexterity task.

为了证明这一点，我们训练猴子 完成一些有关肢体敏捷性的任务。

They had to retrieve food pellets from a tray.

它们需要从盘子里取出食物。

They were very good at it.

它们一向很擅长这种事儿。

And when they had reached a plateau of performance,

当它们的表现稳定后，

we did a lesion in the motor cortex corresponding to the hand motion.

我们在大脑的运动皮层管理手部动作的 区域人为制造了一些损伤。

So the monkeys were plegic,

于是猴子们失去了手部行动能力，

they could not move their hand anymore.

手再也不停使唤了。

And exactly the same as humans would do,

跟人类一样，

they spontaneously recovered to a certain extent,

它们自动恢复到了某种水平，

exactly the same as after a stroke.

跟中风后的情形相同。

Patients are completely plegic,

中风患者完全不具备行动能力，

and then they try to recover due to a brain plasticity mechanism,

他们会试图利用大脑的弹性机制，

they recover to a certain extent,

恢复到某种程度，

exactly the same for the monkey.

猴子也是一样。

So when we were sure that the monkey had reached his plateau

于是当我们很确定猴子的自我恢复能力

of spontaneous recovery,

已经到达极限时，

we implanted his own cells.

我们移植了它自身的细胞。

So on the left side, you see the monkey that has spontaneously recovered.

在左边，你们可以看到 猴子自行恢复的状况。

He's at about 40 to 50 percent of his previous performance

与大脑受到损伤之前的状况相比， 它大概恢复了

before the lesion.

40-50%的行动能力。

He's not so accurate, not so quick.

它的动作不是很精准，也比较慢。

And look now when we re-implant the cells:

再看看现在，我们重新移植了细胞之后：

Two months after re-implantation, the same individual.

同样的个体，移植两个月后的状况。

(Applause)

（掌声）

It was also very exciting results for us, I tell you.

说实话，这样的结果 就连我们也感到很意外。

Since that time, we've understood much more about these cells.

从那时起， 我们对这些细胞就更加了解了。

We know that we can cryopreserve them,

我们知道我们能对 它们进行加密保存，

we can use them later on.

以后也能用得到。

We know that we can apply them in other neuropathological models,

我们也知道我们可以把它们应用到 其他神经病理学模型中，

like Parkinson's disease, for example.

比如帕金森。

But our dream is still to implant them in humans.

但我们始终梦想有一天 能把它们移植入人体中。

And I really hope that I'll be able to show you soon

我真的希望很快就能让你们看到

that the human brain is giving us the tools to repair itself.

人类大脑为我们提供了 让它进行自我修复的工具。

Thank you.

谢谢大家。

(Applause)

（掌声）

Bruno Giussani: Jocelyne, this is amazing,

Bruno Giussaini（BG）: Jocelyne，这太精彩了，

and I'm sure that right now, there are several dozen people in the audience,

现在我很确定，在座的很多人，

甚至可能是大部分人，

possibly even a majority,

都在想，“我知道什么人会需要这项技术。”

who are thinking, "I know somebody who can use this."

I do, in any case.

总之我很确信。

And of course the question is,

当然我还有个问题，

what are the biggest obstacles

在你们能够进行人体临床试验之前，

before you can go into human clinical trials?

你们面临的最大障碍都有哪些呢？

Jocelyne Bloch: The biggest obstacles are regulations. (Laughs)

Jocelyne Bloch （JB）： 最大的障碍就是监管制度。（笑声）

So, from these exciting results, you need to fill out

就是说，有了这些不可思议的结果， 你就得开始处理

about two kilograms of papers and forms

大约两公斤的各种文件和表格，

to be able to go through these kind of trials.

然后才能开始临床试验。

BG：这还算合理吧，毕竟大脑太复杂了， 还有其他种种需要考虑的问题。

BG: Which is understandable, the brain is delicate, etc.

JB: Yes, it is, but it takes a long time

JB：的确，但是这个过程太漫长了，

and a lot of patience and almost a professional team to do it, you know?

需要极度的耐心，还有一个专业团队 来做这个事儿，对吧？

BG: If you project yourself --

BG：如果你们自己立项——

having done the research

自己做研究，

and having tried to get permission to start the trials,

然后试着拿到临床试验的许可，

if you project yourself out in time,

如果能够按时完成这一系列过程，

how many years before somebody gets into a hospital

一个普通人要去医院做这种治疗

and this therapy is available?

还要等上几年呢？

JB: So, it's very difficult to say.

JB：这很难说。

It depends, first, on the approval of the trial.

首先取决于临床试验的批准日期。

Will the regulation allow us to do it soon?

监管机构会让我们尽快开始吗？

And then, you have to perform this kind of study

其次我们还得先在一小部分患者中间

in a small group of patients.

进行预试验。

So it takes, already, a long time to select the patients,

光是挑选合适的患者就要花上一阵子，

do the treatment

还得进行治疗，

and evaluate if it's useful to do this kind of treatment.

再评估这种治疗是否有效。

And then you have to deploy this to a multicentric trial.

之后还要进行多中心治疗。

You have to really prove first that it's useful

我们必须在把这种治疗推广到

before offering this treatment up for everybody.

普通大众身上之前确认它是有效的。

BG: And safe, of course. JB: Of course.

BG：当然还要安全。 JB：肯定的。

BG: Jocelyne, thank you for coming to TED and sharing this.

BG：Jocelyne， 感谢你来TED分享这项研究。

BG：谢谢。

BG: Thank you.

（掌声）

(Applause)