美國科學家制造三維模型模擬大腦功能大綱
A doughnut created in a lab and made of silk on the outside and collagen gel where the jelly ought to be can mimic a basic function of brain tissue, scientists have found.
科學家發現，實驗室裏製造的一個類似甜甜圈的東西，可以模仿腦組織的一項基本功能。這個圓圈的環狀部分由絲材料製成，圈裏面填的是膠原蛋白凝膠。Bioengineers produced a kind of rudimentary gray matter and white matter in a dish, along with rat neurons that signaled one another across the doughnut’s center. When the scientists dropped weights on the material to simulate traumatic injury, the neurons in the three-dimensional brain model emitted chemical and electrical signals similar to those in the brains of injured animals.
生物工程師在培養皿中製成了相當於原始灰質和白質的材料，其中用了大鼠神經元，這些神經元能通過圓圈中間的物質相互交換信號。當科學家讓重物掉到這個圓圈上，以模擬創傷性損傷時，這個三維大腦模型中的神經元釋放出了化學信號和電信號，與受傷動物的大腦釋放的信號類似。
It is the first time scientists have been able to so closely imitate brain function in the laboratory, experts said. If researchers can replicate it with human neurons and enhance it to reflect other neurological functions, it could be used for studying how disease, trauma and medical treatments affect the brain — without the expense and ethical challenges of clinical trials on people.
專家們表示，這是科學家首次能在實驗室裏如此逼真地模仿大腦功能。如果研究人員能用人的神經元重建這個模型，並提升到足以反映其他一些神經系統功能的水平，那麼這個模型或可用於研究疾病、創傷和治療如何影響大腦，從而避免人體臨牀試驗的高費用和倫理問題。
“In terms of mechanical similarity to the brain, it’s a pretty good mimic,” said James J. Hickman, a professor of nanoscience technology at the University of Central Florida, who was not involved in the research. “They’ve been able to repeat the highest level of function of neurons. It’s the best model I’ve seen.”
“從與大腦的機械相似性來看，這是一個相當不錯的模仿，”詹姆斯·J·希克曼(James J. Hickman)說。他是中佛羅里達大學(University of Central Florida)的納米科學與技術教授，沒有參與這項研究。“他們能夠複製出最高水平的神經元功能。這是我看到過的最好的模型。”The research, led by David Kaplan, the chairman of the bioengineering department at Tufts University, and published Monday in the journal PNAS, is the latest example of biomedical engineering being used to make realistic models of organs such as the heart, lungs and liver.
該研究由塔夫茨大學(Tufts University)生物工程系主任戴維·卡普蘭(David Kaplan)主持，於週一發表在《美國科學院院刊》(PNAS)上。這是用生物醫學工程手段製造器官——比如心臟、肺和肝臟——仿真模型的一個最新例子。Most studies of human brain development rely on animals or on brain slices taken after death; both are useful but have limits.
研究人類大腦發育的工作大多依賴於動物實驗，或人死亡後獲取的大腦切片；兩者都有用，但都具侷限性。Brain models have been mostly two-dimensional or made with a three-dimensional gel, said Rosemarie Hunziker, program director of tissue engineering and biomaterial at the National Institute of Biomedical Imaging and Bioengineering, which funded Dr. Kaplan’s research.
美國國家生物醫學成像和生物工程研究所(National Institute of Biomedical Imaging and Bioengineering)的組織工程與生物材料項目主任羅斯瑪麗·亨齊克(Rosemarie Hunziker)稱，以前的大腦模型大多是二維的，或是用三維凝膠製作。該研究所資助了卡普蘭的工作。None of those systems replicate the brain’s gray or white matter, or how neurons communicate, Dr. Hunziker said. “Even if you get cells to live in there, they don’t do much,” she said.
亨齊克還表示，過去的系統都沒有複製大腦的灰質或白質，也沒有複製出神經元如何傳導信號。“就算你能讓細胞在模型中存活，它們基本上也做不成什麼。”Dr. Kaplan’s team found that a spongy silk material coated with a positively charged polymer could culture rat neurons, a stand-in for gray matter. By itself, silk did not encourage neurons to produce axons, branches that transmit electrical pulses to other neurons.
卡普蘭的研究小組發現，一種塗有帶正電聚合物的海綿狀絲製材料可以培養大鼠神經元，用以替代灰質。絲製材料本身並不能讓神經元產生軸突，也就是把電脈衝傳遞給其他神經元的突出部分。The researchers formed the silk material into a doughnut and added collagen gel to the center. Axons grew from the ring through the gel — the white matter substitute — and sent signals to neurons across the circle.
這些研究人員將絲製材料做成一個圓圈，在其中心添加了膠原蛋白凝膠。軸突從圓圈的一邊長出來，通過替代白質的凝膠，把信號發送給圓圈另一邊的神經元。They got “these neurons talking to each other,” Dr. Hunziker said. “No one’s really shown that before.”
亨齊克說，他們讓“這些神經元互相交流。以前沒人真正做到了這一點。”By adding nutrients and growth factors, scientists kept the brainlike tissue alive in an incubator for two months, at which point they experimented on it.
通過添加營養物質和生長因子，科學家把這個類似腦的組織放在孵化器中，讓其存活了兩個月，然後開始在它上面做試驗。Adding a neurotoxin essentially killed the neurons, as it would in a real brain. To simulate traumatic brain injury, they dropped weights from different heights.
添加一種神經毒素基本上會把神經元殺死，就像在真正的大腦中那樣。爲了模擬腦外傷，他們從不同高度讓重物掉到模型上。Dr. Kaplan said the brain-in-a-dish “didn’t go splat,” but reacted like “a kitchen sponge, and it would compress down and then partially spring back up.”
卡普蘭稱，這個培養皿中的大腦“沒有四處飛濺”，其反應更像是“廚房裏的海綿，先是向下壓縮，然後部分反彈起來。”He said measurements of glutamate, a neurotransmitter that surges in injury, showed that “the more severe the damage, the higher the spike” in glutamate.
他說，大腦受傷會導致神經遞質穀氨酸激增，而對模型中谷氨酸的測量顯示，“受傷越重，激增的峯值越高。”Gordana Vunjak-Novakovic, a biomedical engineering professor at Columbia who has worked with Dr. Kaplan on other studies, described the model as a kind of “Lego approach,” a “modular structure” that can be expanded and made more complex.
哥倫比亞大學生物醫學工程系教授戈爾達娜·烏尼亞克-諾瓦科維奇(Gordana Vunjak-Novakovic)曾與卡普蘭在其他研究上有過合作。她稱這個模型的建造有點像“樂高用的方法”，是一種“模塊結構”，可以擴展成更復雜的形態。“It is the first proof of principle that something like this can be achieved outside of the body,” she said.
她說，“這是首次在原理上證明，類似這樣的東西可以在體外實現。”Dr. Hickman said future experiments would need to study other cells and regions in the brain. “They’ve set up an architecture so some clever person in the future could then do it,” he said. Dr. Kaplan said his team was working on sustaining the brainlike tissue for six months — and with human neurons created from stem cells. He plans to add a model of the brain’s vascular system, so researchers can study what happens when drugs cross the blood-brain barrier.
希克曼表示，還需要有未來的實驗來研究大腦的其他細胞和區域。他說，“他們已經建立了一個構架，將來會有聰明人用它來做工作。”卡普蘭稱，他的研究小組正在努力讓這個類似腦的組織存活六個月，還要用上從幹細胞生成的人類神經元。他打算加建一個大腦血管系統的模型，讓研究人員得以觀察當藥物通過血腦屏障時會發生什麼。Ultimately, he hopes the bioengineered model can be used “to study everything from drugs to disease to surgical effects to electrode implants,” he said. “I mean, the list is endless.”
他的最終目標，是讓生物工程模型能被用於“所有的研究，從藥物，到疾病，到手術效果，再到植入電極，”他說。“我的意思是，可做的研究多得沒完沒了。”
