大脑也许可以在辅助下进行自我修复
日期:2017-07-19 18:47

(单词翻译:单击)

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So I'm a neurosurgeon. And like most of my colleagues, I have to deal, every day, with human tragedies.
我是一名神经外科医生。跟我的大多数同事一样,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 after a major stroke or after a car accident.
我认识到一次严重的中风或者一次车祸,就足以在下一秒改变一个人的命运。
And what is very frustrating for us neurosurgeons is to realize that unlike other organs of the body,
对我们这些神经外科医生来说,最难过的事情就是意识到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, the patients often remain with a severe handicap.
在中枢神经系统受到一次严重损伤后,患者将会终身面对严重的残疾。
And that's probably the reason why I've chosen to be a functional neurosurgeon.
这可能也是我想要成为一名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 through different surgical strategies.
他们主要通过各种不同的手术方法来改善神经功能。
You've certainly heard of one of the famous ones called deep brain stimulation,
你们一定听说过很多主流方法中的一个,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 to improve a neurological function.
通过调控神经元电流来改善神经功能。这
It's really an amazing technology in that it has improved the destiny of patients with Parkinson's disease, with severe tremor, with severe pain.
项技术不可思议地扭转了患有帕金森,和被颤抖及疼痛困扰的患者的命运。
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 is to repair the brain.
而功能性神经外科医生希望有朝一日能够修复受损的大脑。
I think that we are approaching this dream.
我认为我们正在一步步接近这个目标。
And I would like to show you that we are very close to this.
我想让大家看看我们离成功已经近在咫尺了。
And that with a little bit of help, the brain is able to help itself.
只需要一点点的人工辅助,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 working days and nights in the emergency room.
那时候我还是一名住院总医师,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 and he's increasing his intracranial pressure.
他的大脑不断肿胀,颅内压越来越高。
And in order to save his life, you have to decrease this intracranial pressure.
要挽救他的生命,就必须要降低颅内压。
And to do that, you sometimes have to remove a piece of swollen brain.
要做到这一点,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-Francois Brunet, who is a colleague of mine, a biologist, to study them.
而是在与生物学家,也是我的一位同事Jean-Francois Brunet商量之后,决定对这部分组织进行进一步研究。
What do I mean by that? We wanted to grow cells from these pieces of tissue. It's not an easy task.
具体要怎么研究呢?我们想让这一部分组织长出细胞来。这可不是件容易的事儿。
Growing cells from a piece of tissue is a bit the same as growing very small children out from their family.
让组织生长出细胞,就好比一个家庭开始养育一个小宝宝。
So you need to find the right nutrients, the warmth, the humidity and all the nice environments to make them thrive.
需要找到合适的营养成分,合适的温度和湿度,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, Jean-Francois did it. And that's what he saw under his microscope.
尝试过很多次之后,Jean-Francois成功了。这就是他在显微镜下看到的一幕。
And that was, for us, a major surprise. Why?
对我们来说,这是个天大的惊喜。为什么呢?
Because this looks exactly the same as a stem cell culture, with large green cells surrounding small, immature cells.
因为这看起来跟干细胞群落几乎一模一样,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 that stem cells are immature cells, able to turn into any type of cell of the body.
你们可能还记得生物课上讲过,干细胞是未发育成熟的细胞,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 and they're located in deep and small niches in the depths of the brain.
成人的大脑也有干细胞,但是数量很少,而且分布于大脑深处隐蔽的角落里。
So it was surprising to get this kind of stem cell culture from the superficial part of swollen brain we had in the operating theater.
所以能够在操作室里从肿胀的大脑表面获得这种干细胞群落,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 -- cells that divide, divide, divide very quickly.
正常的干细胞非常活跃--它们可以不断地进行快速分裂。
And they never die, they're immortal cells. But these cells behave differently.
它们也不会凋亡,能够一直存活。但是这些细胞却有着不同的行为。
They divide slowly, and after a few weeks of culture, they even died.
它们分裂得很慢,而且仅仅过了几个星期,就会慢慢死掉。
So we were in front of a strange new cell population that looked like stem cells but behaved differently.
于是我们面前就出现了一个奇怪的新的细胞群落,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. They come from these cells.
我们花了好长时间才搞清楚它们是从哪儿来的。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阳性细胞。

大脑也许可以在辅助下进行自我修复

All of you have them in your brain. They represent four percent of your cortical brain cells.
它们存在于我们每个人的大脑中,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, they helped your brain to fold itself.
在婴儿时期,它们能帮助大脑产生褶皱。
But why do they stay in your head? This, we don't know.
但它们为什么会一直留在大脑中呢?这一点我们还不清楚。
We think that they may participate in brain repair because we find them in higher concentration close to brain lesions.
我们认为它们可能参与了大脑修复,是因为我们发现在大脑损伤的部位它们的浓度比较高。
But it's not so sure. But there is one clear thing -- that from these cells, we got our stem cell culture.
但我们还不是非常确定。但有一点已经很清楚了--也就是从这些细胞中,我们得到了干细胞群落。
And we were in front of a potential new source of cells to repair the brain. And we had to prove this.
我们面前正是一群有可能修复大脑的细胞的新来源。我们需要证明这一点。
So to prove it, we decided to design an experimental paradigm.
那么想要证明,我们决定设计一组对照试实验。
The idea was to biopsy a piece of brain in a non-eloquent area of the brain,
基本概念就是在大脑中一块功能尚不明确的区域进行活组织提取,
and then to culture the cells exactly the way Jean-Francois did it in his lab.
然后用Jean-Francois在实验室尝试过的同样的方法培养细胞。
And then label them, to put color in them in order to be able to track them in the brain.
然后给它们做标记,染色,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 in the same individual.
最后一步就是把它们重新移植入相同的个体中。
We call these autologous grafts -- autografts.
我们把这叫做自体同源嫁接--自嫁接。
So the first question we had, "What will happen if we re-implant these cells in a normal brain,
我们的第一个问题就是,“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 in a lesioned brain?"
或者一个受过损伤的大脑,会有什么区别呢?”
Thanks to the help of professor Eric Rouiller, we worked with monkeys.
很幸运,在Eric Rouiller教授的帮助下,我们得以在猴子身上进行试验。
So in the first-case scenario, we re-implanted the cells in the normal brain
在第一种情况中,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, as if they were taken from the brain,
发现它们在仅仅几周后就完全消失了,就好像被从大脑中清除了一样,
they go back home, the space is already busy, they are not needed there, so they disappear.
它们被驱赶出了这一区域,这里没有多余的空间了,它们发挥不了任何作用,于是就消失了。
In the second-case scenario, we performed the lesion, we re-implanted exactly the same cells,
在第二种情况中,我们用了受损的大脑,把一模一样的细胞移植了进去,
and in this case, the cells remained -- and they became mature neurons.
而这一次,细胞存活了下来--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. And the proof they carry, these little spots,
这些是重新移植过的细胞。证据表明,这些小点
those are the cells that we've labeled in vitro, when they were in culture.
就是我们在体外标记过的还处在群落状态下的细胞。
But we could not stop here, of course. Do these cells also help a monkey to recover after a lesion?
但这肯定还远远不够。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. They were very good at it.
它们需要从盘子里取出食物。它们一向很擅长这种事儿。
And when they had reached a plateau of performance, we did a lesion in the motor cortex corresponding to the hand motion.
当它们的表现稳定后,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, they could not move their hand anymore.
于是猴子们失去了手部行动能力,手再也不停使唤了。
And exactly the same as humans would do, they spontaneously recovered to a certain extent, exactly the same as after a stroke.
跟人类一样,它们自动恢复到了某种水平,跟中风后的情形相同。
Patients are completely plegic, and then they try to recover due to a brain plasticity mechanism,
中风患者完全不具备行动能力,他们会试图利用大脑的弹性机制,
they recover to a certain extent, exactly the same for the monkey.
恢复到某种程度,猴子也是一样。
So when we were sure that the monkey had reached his plateau of spontaneous recovery, we implanted his own cells.
于是当我们很确定猴子的自我恢复能力已经到达极限时,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 before the lesion.
与大脑受到损伤之前的状况相比,它大概恢复了40-50%的行动能力。
He's not so accurate, not so quick. And look now when we re-implant the cells:
它的动作不是很精准,也比较慢。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。
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, we can use them later on.
我们知道我们能对它们进行加密保存,以后也能用得到。
We know that we can apply them in other neuropathological models, like Parkinson's disease, for example.
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,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 that the human brain is giving us the tools to repair itself. Thank you.
我真的希望很快就能让你们看到人类大脑为我们提供了让它进行自我修复的工具。谢谢大家。
Jocelyne, this is amazing, and I'm sure that right now, there are several dozen people in the audience,
Jocelyne,这太精彩了,现在我很确定,在座的很多人,
possibly even a majority, who are thinking, "I know somebody who can use this." I do, in any case.
甚至可能是大部分人,都在想,“我知道什么人会需要这项技术。”总之我很确信。
And of course the question is, what are the biggest obstacles before you can go into human clinical trials?
当然我还有个问题,在你们能够进行人体临床试验之前,你们面临的最大障碍都有哪些呢?
The biggest obstacles are regulations. So, from these exciting results,
最大的障碍就是监管制度。就是说,有了这些不可思议的结果,
you need to fill out about two kilograms of papers and forms to be able to go through these kind of trials.
你就得开始处理大约两公斤的各种文件和表格,然后才能开始临床试验。
Which is understandable, the brain is delicate, etc.
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。
Yes, it is, but it takes a long time and a lot of patience and almost a professional team to do it, you know?
的确,但是这个过程太漫长了,需要极度的耐心,还有一个专业团队来做这个事儿,对吧?
If you project yourself -- having done the research and having tried to get permission to start the trials,
如果你们自己立项--自己做研究,然后试着拿到临床试验的许可,
if you project yourself out in time, how many years before somebody gets into a hospital and this therapy is available?
如果能够按时完成这一系列过程,一个普通人要去医院做这种治疗还要等上几年呢?
So, it's very difficult to say. It depends, first, on the approval of the trial.
这很难说。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 in a small group of patients.
其次我们还得先在一小部分患者中间进行预试验。
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 and evaluate if it's useful to do this kind of treatment.
还得进行治疗,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 before offering this treatment up for everybody.
我们必须在把这种治疗推广到普通大众身上之前确认它是有效的。
And safe, of course. Of course.
当然还要安全。肯定的。
Jocelyne, thank you for coming to TED and sharing this. Thank you.
Jocelyne,感谢你来TED分享这项研究。谢谢。

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