Pig brains partially restored by scientists hours after death of animals: shots



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The image on the left shows pig brains that have not been treated for 10 hours after death, neurons appear green, astrocytes red and cell nuclei blue. The right image shows cells located in the same brain area that, four hours after his death, were connected to a system called Brain by researchers at Yale University.Ex.

Stefano G. Daniele and Zvonimir Vrselja, Sestan Laboratory, Yale School of Medicine


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Stefano G. Daniele and Zvonimir Vrselja, Sestan Laboratory, Yale School of Medicine

The image on the left shows pig brains that have not been treated for 10 hours after death, neurons appear green, astrocytes red and cell nuclei blue. The right image shows cells located in the same brain area that, four hours after his death, were connected to a system called Brain by researchers at Yale University.Ex.

Stefano G. Daniele and Zvonimir Vrselja, Sestan Laboratory, Yale School of Medicine

Scientists have rekindled the brains of dead pigs a few hours after being slaughtered in a slaughterhouse.

The research team at Yale University ensures that no brain finds the type of organized electrical activity associated with consciousness or consciousness. Yet, the experiment described Wednesday in the newspaper Nature showed that a surprising amount of cellular function was either preserved or restored.

Ethicists have astonished the implications of this study, as they reflect on how this research should progress and its integration into the current understanding of what separates the living from the dead.

"It was breathtaking," says Nita Farahany, who is studying Emerging Technologies Ethics at Duke Law School. "My initial reaction was quite shocked.It is a breakthrough discovery, but it also fundamentally alters much of the existing belief in neuroscience regarding the irreversible loss of brain function once the brain is deprived of the brain. ;oxygen."

The brain is extremely sensitive to lack of oxygen and stops quickly. Nenad Sestan, a neuroscientist at Yale School of Medicine in New Haven, Connecticut, says researchers have long known that viable cells can be removed from the post-mortem brain within hours of death.

Such cells can be studied in a lab dish, says Sestan, "but the problem is that once you do that, you lose the 3D brain organization."

With some colleagues, he wondered whether it would be possible to study brain cells by leaving them in an intact organ. This meant somehow providing them with oxygen, nutrients and various other protective chemicals from the cells.

Over the last six years, scientists have developed a technique to test their methods on approximately 300 pork heads obtained from a local pork processing center.

"It was really a project filmed in the dark," said Stefano Daniele, a member of the team. "We had no preconceived idea of ​​whether it could work or not."

After deciding on the final version of their technology, what they call BrainEx, they did a detailed study using 32 pork heads. Daniele recounts that when he was at the slaughterhouse, he and his research colleague, Zvonimir Vrselja, had emptied the brain to remove residual blood and cool the tissues.

Back in the lab, they removed the brains from the pigs' heads and isolated them in an experimental chamber. The researchers hooked vital blood vessels to a device that injected a specially formulated chemical cocktail for six hours, starting about four hours after the pigs were killed.

These brains finally seemed radically different from the pork brains left on their own to deteriorate. "We have found that the structure of tissues and cells is preserved and cell death is reduced, and some molecular and cellular functions have been restored," Sestan said. "It's not a living brain, but it's an active brain on a cellular level."

The researchers' approach offers a new way to study brain diseases or lesions in the laboratory and to explore the fundamental biology of the brain. "We could actually answer questions we can not now," says Vrselja.

"This is a breakthrough for brain research and is a new tool to bridge the gap between fundamental neuroscience and clinical research," says Andrea Beckel-Mitchener. of the National Institute of Mental Health, which collaborates with the BRAIN initiative. The BRAIN initiative, launched in 2013 to accelerate research in neuroscience, funded the work.

The researchers pointed out that the goal was by no means to restore awareness in these pig brains. "It was something that actively concerned researchers," says Stephen Latham, Yale bioethicist who worked with the team.

Scientists have continuously monitored the electrical activity of pigs' brains, says Latham. If they had seen any evidence that signals associated with consciousness had emerged, they would have used anesthesia and cooling to immediately stop this activity.

"And the reason is that they did not want to do an experiment that raises the ethical issues that would arise if consciousness was evoked in that brain," says Latham, "without first having received some sort of serious ethical direction."

The special solution injected into the brain included lamotrigine, an anti-epileptic drug known to block or lessen neuronal activity. This is because "the researchers thought that brain cells could be better preserved and their function could be better restored if they were not active," said Latham.

But tests on individual cells taken from porcine brain, involving the washing of the solution, showed that the individual cells were capable of electrochemical responses. It is therefore unclear whether the team could have seen an overall electrical activity related to consciousness in the pig brain if the blocker of neuronal activity had been left out of treatment or if the blocker had been removed after the treatment. partial regeneration of the cells.

"This is a very important question, and we have discussed it at length," says Daniele. "We can not speak with any scientific certainty at this point because we have not conducted these experiments."

The potential ethical issues raised by this research range from the protection of animal welfare to how it could affect the donation of organs of people who have been declared deadly brain.

"Science is so new that we all need to work together to think proactively about its ethical implications, so that we can responsibly shape the way this science evolves," said Khara Ramos, director of the neuroethics program at the University of California. National Institute of Neurological Disorders. Stroke.

A few years ago, Yale researchers consulted a working group on neuroethics organized by the BRAIN initiative of the National Institutes of Health. That's how Farahany learned the research. She says these results need to be replicated in other labs to see if they are resisting.

But if they do, the results challenge many of the assumptions underlying the legal and ethical controls of the experiments.

"If it's a dead animal, it's not subject to any protection from research because you would not expect it to suffer from pain or distress or of the need to consider it as a human care, "says Farahany. But if the brain of this animal can be even partially restored, she asks, "what should we do immediately, today, to ensure the establishment of adequate protections for animal research subjects? "

In addition, she adds, "people will immediately recognize the potential of this research.It is actually possible to restore the cellular activity of brain tissue that we thought was irretrievably lost in the past. it goes without saying that wanting to apply this ultimately to the man. "

Although there are safeguards in place for human research subjects, this is not so much the case for dead human tissue, says Christine Grady, head of the bioethics department at NIH Clinical Center.

"Once a human dies and his tissues are in a lab, there are far fewer restrictions on what can be done," says Grady. "It is interesting to think about this question in the light of this experience."

In a commentary that accompanied the research paper in NatureFarahany and colleagues Henry Greely and Charles Giattino say their work reminds them of a replica of the 1987 film The princess to marry"There is a big difference between most deaths and deaths, most of the dead are slightly alive."

Research like this could complicate efforts to get organs for the transplantation of people who have been declared brain dead, according to another commentary by Case Western Reserve University bioethicians Stuart Youngner and Insoo Hyun.

If people who have been declared brain dead can become candidates for brain resuscitation, they write, "it may be more difficult for doctors or family members to be convinced that any other medical intervention is futile."

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