The restoration of some structures and cellular functions in pig brains hours after death could intensify debates about when human organs should be removed for transplantation
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Researchers describe restoring certain structural and functional properties to pigs’ brains, as reported in the journal Nature, even four hours after the animals had been killed. They used an artificial perfusion system called BrainEx. Electrophysiological monitoring did not detect any kind of neural activity thought to signal consciousness, such as any evidence of signalling between brain regions. Nonetheless, the study challenges the long-held assumption that large mammalian brains are irreversibly damaged a few minutes after blood stops circulating. It also raises the possibility that researchers could get better at salvaging a person’s brain even after the heart and lungs have stopped working.

The pigs were acquired from a food processing plant near New Haven, Connecticut after the animals had already been killed for their meat. They were able to restore cellular function in 32 pig brains.

Clinically defined, this is not a living brain, study co-author Nenad Sestan told National Geographic. Sestan is a neuroscientist at the Yale University School of Medicine.

Pig experiment challenges assumptions around brain damage in people  /  image by Roy Buri  /  source  /  license CC0

Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.

The researchers are quick to clarify that issue. The idea isn’t necessarily to bring pigs — or people — back from the dead. The most immediate and practical application is for patients who suffered strokes or heart attacks or anything else that might have restricted blood and oxygen flow to the brain.

We’re really excited about this as a platform that could help us better understand how to treat people who have had heart attacks and have lost normal blood flow to the brain, Khara Ramos, director of the Neuroethics Program at the U.S. National Institute of Neurological Disorders and Stroke, told National Geographic. It really enhances our ability to study cells as they exist in connection with each other, in that three-dimensional, large, complicated way.

Researchers hope to further our understanding of the brain  /  image by Skeeze  /  source  /  license CC0

The restoration of some structures and cellular functions in pig brains hours after death could intensify debates about when human organs should be removed for transplantation.

But the story is dramatic in itself, somewhat challenging the idea of what death is by questioning the finality of brain death. A Nature article about the research, however, points out that, “Although the experiments stopped short of restoring consciousness, they raised questions about the ethics of the approach — and, more fundamentally, about the nature of death itself. The current legal and medical definitions of death guide protocols for resuscitating people and for transplanting organs.”

The BrainEx device pumped a blood substitute into the pig brains. It restored some functions, such as the cells’ ability to produce energy and remove waste. It also helped maintain the brains’ internal structure.

As Nature points out, in most countries around the world, the legal definition of death is when brain activity stops or when the heart and lungs stop working. Although the use of ventilators has kept some patients alive past the point where brain death is evident, all moral, ethical and legal issues revolving around this have not been fully defined or resolved.

In their research, Sestan and his team removed each brain from its skull and inserted them into a special chamber. They then fitted the brains with a catheter. Four hours after death, they pumped a warm preservative solution into the veins and arteries in the brain. The preservative solution held chemicals that stop neurons from firing, which protects them from damage and prevents brain electrical activity from restarting. They monitored the brain activity and would have administered anesthetics if the saw any indications the brains might regain consciousness.

The study evaluated how the brains performed over a six-hour period. Even after six hours, when they stimulated brain tissue with electricity, the individual neurons still carried a signal. The cell structures were preserved and normal metabolic functions like sugar consumption and the production of carbon dioxide remained.

Brain dead organ donor during operation  /  image by Rodolfo Buhrer, Reuters  /  source

Surgeons in Berlin operate on a woman who has been declared brain dead to remove her liver and kidneys for transplantation.

However, the scientists did not see coordinated electrical patterns across the entire brain. This would have suggested “sophisticated brain activity or even consciousness.” They suspect that restarting brain activity would require an electrical shock or other types of chemical solutions to preserve the brain in a way that would allow cells from repair themselves from oxygen deprivation. The team has no immediate plans to attempt to restore full electrical activity in pig brains.

Sestan also says they don’t know how long the brain activity can be sustained. They kept the pig brains alive for up to 36 hours. He told Nature, “It is conceivable we are just preventing the inevitable, and the brain won’t be able to recover. We just flew a few hundred meters, but can we really fly?”

And the BrainEx system is nowhere near being able to be used in human beings. One reason is simple enough—it would first require removing the brain from the skull. But there are broad ethical issues to be addressed first, let alone the technical issues.

Stephen Latham a Yale bioethicist who worked with Sestan’s team, told Nature, “There isn’t really an oversight mechanism in place for worrying about the possible ethical consequences of creating consciousness in something that isn’t a living animal.”

But at the very least, the study raises questions about whether brain damage and death are permanent. Although there are significant short-term implications for organ donation technologies and questions about how and when to classify breath death, the research opens an entire universe of opportunities for potential treatments for patients with brain injury.

Source and references

  1. by Michael Greshko - Pig brains partially revived hours after death—what it means for people
  2. Stuart Youngner and Insoo Hyun - Pig experiment challenges assumptions around brain damage in people
  3. - Restoration of brain circulation and cellular functions hours post-mortem
  4. - Part-revived pig brains raise slew of ethical quandaries
  5. - Extracorporeal membrane oxygenation (ECMO) assisted cardiopulmonary resuscitation
  6. by Steve Gorman - Yale study revives cellular activity in pig brains hours after death
  7. - The Rise and Fall of the Futility Movement
  8. - Circulatory Death Determination in Uncontrolled Organ Donors: A Panel Viewpoint
  9. - Protocols for uncontrolled donation after circulatory death: a systematic review of international guidelines, practices and transplant outcomes
  10. - CEASE: A Guide for Clinicians on How to Stop Resuscitation Efforts
  11. - Determining Death in Uncontrolled DCDD Organ Donors
  12. - Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study
  13. - A Rationale in Support of Uncontrolled Donation after Circulatory Determination of Death
  14. - Extracorporeal Support for Organ Donation after Cardiac Death Effectively Expands the Donor Pool
  15. - Extracorporeal membrane oxygenation support of donor abdominal organs in non‐heart‐beating donors
  16. by Mark Terry - Yale Scientists Restore Brain Activity in Dead Pigs Hours After Death
  17. By Rachael Rettner - Hours After Pigs' Death, Scientists Restore Brain Cell Activity
  18. Kevin Dickinson - Yale scientists restore brain function to 32 clinically dead pigs
  19. - Electrophysiology

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Last updated 3 years ago on July 01, 2019 at 12:52 PM PDT

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