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大脑超强的可塑性

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

我是一名神经外科医生
So I’m a neurosurgeon.
跟大多数同事一样
And like most of my colleagues,
我每天都要面对各种人世间的悲剧
I have to deal, every day, with human tragedies.
我认识到一次严重的车祸或者一次中风
I realize how your life can change from one second to the other
就足以在下一秒改变一个人的命运
after a major stroke or after a car accident.
对我们这些神经外科医生来说 最难过的事情就是意识到
And what is very frustrating for us neurosurgeons
与其他身体器官不同
is to realize that unlike other organs of the body,
大脑几乎不能进行自我修复
the brain has very little ability for self-repair.
在中枢神经系统受到一次严重损伤后
And after a major injury of your central nervous system,
患者将会终身面对严重的残疾
the patients often remain with a severe handicap.
这可能也是我想要成为一名
And that’s probably the reason why I’ve chosen
功能性神经外科医生的原因
to be a functional neurosurgeon.
功能性神经外科医生是做什么的?
What is a functional neurosurgeon?
他们主要通过各种不同的手术方法
It’s a doctor who is trying to improve a neurological function
来改善神经功能
through different surgical strategies.
你们一定听说过很多主流方法中的一个
You’ve certainly heard of one of the famous ones
叫做深度脑电刺激
called deep brain stimulation,
通常是把一个电极植入大脑深处
where you implant an electrode in the depths of the brain
通过调控神经元电流
in order to modulate a circuit of neurons
来改善神经功能
to improve a neurological function.
这项技术不可思议地
It’s really an amazing technology
扭转了患有帕金森
in that it has improved the destiny of patients
和被颤抖及疼痛困扰的
with Parkinson’s disease,
患者的命运
with severe tremor, with severe pain.
但是神经调控并不意味着神经元的修复
However, neuromodulation does not mean neuro-repair.
而功能性神经外科医生希望有朝一日
And the dream of functional neurosurgeons
能够修复受损的大脑
is to repair the brain.
我认为
I think
我们正在一步步接近这个目标
that we are approaching this dream.
我想让大家看看
And I would like to show you
我们离成功已经近在咫尺了
that we are very close to this.
只需要一点点的人工辅助
And that with a little bit of help,
大脑就可以进行自我修复
the brain is able to help itself.
事情还要从15年前说起
So the story started 15 years ago.
那时候我还是一名住院总医师
At that time, I was a chief resident
夜以继日地在急诊室忙碌
working days and nights in the emergency room.
我经常要护理有大脑损伤的病患
I often had to take care of patients with head trauma.
你们可以想象一下 带有严重脑外伤的患者被推进来
You have to imagine that when a patient comes in with a severe head trauma,
他的大脑不断肿胀
his brain is swelling
颅内压越来越高
and he’s increasing his intracranial pressure.
要挽救他的生命
And in order to save his life,
就必须要降低颅内压
you have to decrease this intracranial pressure.
要做到这一点
And to do that,
有时候就需要移除一部分肿胀的脑组织
you sometimes have to remove a piece of swollen brain.
不过我们并没有把这一部分 肿胀的大脑直接丢弃
So instead of throwing away these pieces of swollen brain,
而是与我的一位同事
we decided with Jean-François Brunet,
生物学家Jean-François Brunet一起
who is a colleague of mine, a biologist,
决定对这部分组织进行更深层次的研究
to study them.
具体要怎么研究呢?
What do I mean by that?
我们想让这一部分组织长出细胞来
We wanted to grow cells from these pieces of tissue.
这可不是件容易的事儿
It’s not an easy task.
让组织生长出细胞
Growing cells from a piece of tissue
就好比一个家庭开始
is a bit the same as growing very small children
养育一个小宝贝
out from their family.
需要找到合适的营养成分
So you need to find the right nutrients,
温度、湿度
the warmth, the humidity
和所有适宜的环境条件让他们茁壮成长起来
and all the nice environments to make them thrive.
这正是我们培养这些细胞需要做的
So that’s exactly what we had to do with these cells.
尝试过很多次之后
And after many attempts,
Jean-François成功了
Jean-François did it.
这就是他在显微镜下看到的一幕
And that’s what he saw under his microscope.
对我们来说 这是个天大的惊喜
And that was, for us, a major surprise.
为什么呢?
Why?
因为这看起来跟干细胞群落 几乎一模一样
Because this looks exactly the same as a stem cell culture,
小的尚未成熟的细胞被一大群 绿色较大的细胞包围着
with large green cells surrounding small, immature cells.
你们可能还记得生物课上讲过
And you may remember from biology class
干细胞是未发育成熟的细胞
that stem cells are immature cells,
可以演变成人体的任何一种细胞
able to turn into any type of cell of the body.
成人的大脑也有干细胞 但是数量很少
The adult brain has stem cells, but they’re very rare
而且分布于大脑深处
and they’re located in deep and small niches
隐蔽的角落里
in the depths of the brain.
所以能够在操作室里从肿胀的
So it was surprising to get this kind of stem cell culture
大脑表面获得这种干细胞群落
from the superficial part of swollen brain we had
真是太让人意外了
in the operating theater.
而我们还观察到了 另外一个有趣的现象:
And there was another intriguing observation:
正常的干细胞非常活跃
Regular stem cells are very active cells —
它们可以不断地进行快速分裂
cells that divide, divide, divide very quickly.
它们也不会凋亡 能够一直存活
And they never die, they’re immortal cells.
但是这些细胞却有着不同的行为
But these cells behave differently.
它们分裂得很慢
They divide slowly,
而且仅仅过了几个星期
and after a few weeks of culture,
就会慢慢死掉
they even died.
于是我们面前就出现了 一个奇怪的新的细胞群落
So we were in front of a strange new cell population
看起来像干细胞 但其行为却又跟干细胞有着天壤之别
that looked like stem cells but behaved differently.
我们花了好长时间 才搞清楚它们是从哪儿来的
And it took us a long time to understand where they came from.
它们来自于这些细胞
They come from these cells.
这些蓝色和红色的细胞称为双皮质素-阳性细胞
These blue and red cells are called doublecortin-positive cells.
它们存在于我们每个人的大脑中
All of you have them in your brain.
组成了我们4%的大脑皮层细胞
They represent four percent of your cortical brain cells.
在大脑发育过程中 这些细胞起着至关重要的作用
They have a very important role during the development stage.
在婴儿时期
When you were fetuses,
它们能帮助大脑产生褶皱
they helped your brain to fold itself.
但它们为什么会一直留在大脑中呢?
But why do they stay in your head?
这一点我们还不清楚
This, we don’t know.
我们认为它们可能参与了大脑修复
We think that they may participate in brain repair
是因为我们发现在大脑损伤的部位
because we find them in higher concentration
它们的浓度比较高
close to brain lesions.
但我们还不是非常确定
But it’s not so sure.
但有一点已经很清楚了
But there is one clear thing —
也就是从这些细胞中
that from these cells,
我们得到了干细胞群落
we got our stem cell culture.
我们面前正是一群有可能修复大脑的
And we were in front of a potential new source of cells
细胞的新来源
to repair the brain.
我们需要证明这一点
And we had to prove this.
那么想要证明
So to prove it,
我们决定设计一组对照试实验
we decided to design an experimental paradigm.
基本概念就是在大脑中一块
The idea was to biopsy a piece of brain
功能尚不明确的区域进行活组织提取
in a non-eloquent area of the brain,
然后用Jean-François在实验室
and then to culture the cells
尝试过的同样的方法培养细胞
exactly the way Jean-François did it in his lab.
然后给它们做标记染色
And then label them, to put color in them
这样就可以在大脑中追踪它们的活动
in order to be able to track them in the brain.
最后一步就是把它们重新移植入
And the last step was to re-implant them
相同的个体中
in the same individual.
我们把这叫做
We call these
自体同源嫁接 自嫁接
autologous grafts — autografts.
我们的第一个问题就是
So the first question we had,
如果我们把这些细胞 重新植入进一个正常的大脑
“What will happen if we re-implant these cells in a normal brain,
或者一个受过损伤的大脑
and what will happen if we re-implant the same cells
会有什么区别呢?
in a lesioned brain?”
很幸运 在Eric Rouiller教授的帮助下
Thanks to the help of professor Eric Rouiller,
我们得以在猴子身上进行试验
we worked with monkeys.
在第一种情况中
So in the first-case scenario,
我们把这些细胞移植入了正常大脑中
we re-implanted the cells in the normal brain
发现它们在仅仅几周后就完全消失了
and what we saw is that they completely disappeared after a few weeks,
就好像被从大脑中清除了一样
as if they were taken from the brain,
它们被驱赶出了这一区域
they go back home,
这里没有多余的空间了
the space is already busy,
它们发挥不了任何作用 于是就消失了
they are not needed there, so they disappear.
在第二种情况中
In the second-case scenario,
我们用了受损的大脑
we performed the lesion,
把一模一样的细胞移植了进去
we re-implanted exactly the same cells,
而这一次 细胞存活了下来
and in this case, the cells remained —
它们发育成了成熟的神经细胞
and they became mature neurons.
这就是我们在显微镜下看到的图像
And that’s the image of what we could observe under the microscope.
这些是重新移植过的细胞
Those are the cells that were re-implanted.
证据表明
And the proof they carry,
这些小点就是我们在体外标记过的
these little spots, those are the cells that we’ve labeled
还处在群落状态下的细胞
in vitro, when they were in culture.
但这肯定还远远不够
But we could not stop here, of course.
那么这些细胞到底会不会 修复猴子的脑损伤呢?
Do these cells also help a monkey to recover after a lesion?
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
So for that, we trained monkeys to perform a manual dexterity task.
它们需要从盘子里取出食物
They had to retrieve food pellets from a tray.
它们一向很擅长这种事儿
They were very good at it.
当它们的表现稳定后
And when they had reached a plateau of performance,
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
we did a lesion in the motor cortex corresponding to the hand motion.
于是猴子们失去了手部行动能力
So the monkeys were plegic,
手再也不停使唤了
they could not move their hand anymore.
跟人类一样
And exactly the same as humans would do,
它们自动恢复到了某种水平
they spontaneously recovered to a certain extent,
跟中风后的情形相同
exactly the same as after a stroke.
中风患者完全不具备行动能力
Patients are completely plegic,
他们会试图利用大脑的弹性机制
and then they try to recover due to a brain plasticity mechanism,
恢复到某种程度
they recover to a certain extent,
猴子也是一样
exactly the same for the monkey.
于是当我们很确定猴子的自我恢复能力
So when we were sure that the monkey had reached his plateau
已由最活跃进入稳定期时
of spontaneous recovery,
我们移植了它自身的细胞
we implanted his own cells.
在左边 你们可以看到猴子自行恢复的状况
So on the left side, you see the monkey that has spontaneously recovered.
它大概恢复到了受伤之前正常行为表现的
He’s at about 40 to 50 percent of his previous performance
40-50%的能力
before the lesion.
它的动作不是很精准 也比较慢
He’s not so accurate, not so quick.
再看看现在我们重新移植了细胞之后:
And look now when we re-implant the cells:
同样的个体 移植两个月后的状况
Two months after re-implantation, the same individual.
(掌声)
(Applause)
说实话 这样的结果就连我们也感到很意外
It was also very exciting results for us, I tell you.
从那时起 我们对这些细胞就更加了解了
Since that time, we’ve understood much more about these cells.
我们知道我们能对它们进行加密保存
We know that we can cryopreserve them,
我们可以将来再用
we can use them later on.
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
We know that we can apply them in other neuropathological models,
比如帕金森
like Parkinson’s disease, for example.
但我们始终梦想有一天 能把它们移植入人体中
But our dream is still to implant them in humans.
我真的希望很快就能让你们看到
And I really hope that I’ll be able to show you soon
人类大脑为我们提供了 能让它自行修复的工具
that the human brain is giving us the tools to repair itself.
谢谢大家
Thank you.
(掌声)
(Applause)
Bruno Giussaini(BG): Jocelyne 这太精彩了
Bruno Giussani: Jocelyne, this is amazing,
现在我很确定 在座的很多人
and I’m sure that right now, there are several dozen people in the audience,
甚至是大部分人
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.”
总之我很确信
I do, in any case.
当然我还有个问题
And of course the question is,
在你们能够进行人体临床试验之前
what are the biggest obstacles
你们面临的最大障碍都有哪些呢?
before you can go into human clinical trials?
Jocelyne Bloch (JB):最大的障碍就是监管制度(笑声)
Jocelyne Bloch: The biggest obstacles are regulations. (Laughs)
就是说 有了这些不可思议的结果 你就得开始处理
So, from these exciting results, you need to fill out
大约两公斤的各种文件和表格
about two kilograms of papers and forms
然后才能开始临床试验
to be able to go through these kind of trials.
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:的确 但是这个过程太漫长了
JB: Yes, it is, but it takes a long time
需要极度的耐心 还有一个专业团队来做这个事儿 对吧?
and a lot of patience and almost a professional team to do it, you know?
BG:如果你们自己立项
BG: If you project yourself —
自己做研究
having done the research
然后试着拿到临床试验的许可
and having tried to get permission to start the trials,
如果能够按时完成这一系列过程
if you project yourself out in time,
一个普通人要去医院做这种治疗
how many years before somebody gets into a hospital
还要等上几年呢?
and this therapy is available?
JB:这很难说
JB: So, it’s very difficult to say.
首先取决于临床试验的批准日期
It depends, first, on the approval of the trial.
监管机构会让我们尽快开始吗?
Will the regulation allow us to do it soon?
其次我们还得先在一小部分患者中间
And then, you have to perform this kind of study
进行预试验
in a small group of patients.
光是挑选合适的患者就要花上一阵子
So it takes, already, a long time to select the patients,
还得进行治疗
do the treatment
再评估这种治疗是否有效
and evaluate if it’s useful to do this kind of treatment.
之后还要进行多中心治疗
And then you have to deploy this to a multicentric trial.
我们必须在把这种治疗推广到
You have to really prove first that it’s useful
普通大众身上之前确认它是有效的
before offering this treatment up for everybody.
BG:当然还要安全 JB:肯定的
BG: And safe, of course. JB: Of course.
BG:Jocelyne 感谢你来TED分享这项研究
BG: Jocelyne, thank you for coming to TED and sharing this.
BG:谢谢你
BG: Thank you.
(掌声)
(Applause)

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视频概述

对于车祸等意外造成的脑损伤,大脑不能自我修复,我们验证的物理刺激,细胞培养比较超前,但这也许是复杂大脑自我修复的应对办法

听录译者

收集自网络

翻译译者

Ljimnn

审核员

瞌睡虫儿

视频来源

https://www.youtube.com/watch?v=6d6oq0zGGmw

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