Researchers 'reboot' pig brains hours after animals died
The brains of decapitated pigs can be partially revived several hours after the animal has died, researchers have revealed, with some of the functions of cells booted back up when an oxygen-rich fluid is circulated through the organ.
The scientists stress that the brains do not show any signs of consciousness – for example, there was no sign that different parts of the brain were sending signals to each other – and that it does not change the definition of death.
But they say they have found a way to prevent brain cells from sustaining irreparable damage as blood stops circulating, and even to restore some of the cells’ functions.
“This is not a living brain. But it is a cellularly active brain,” said Prof Nenad Sestan from Yale University, who led the research.
Sestan added that the results had exceeded expectations. “When we started this study we really never imagined we would get to this point,” he said.
The team said the approach could provide a new way to study the brain, and even help in the development and testing of new therapies for stroke and other conditions in which bloodflow to parts of the brain is blocked, causing cells to die.
A number of studies, including those involving cells taken from dead brains, have suggested brain cells might not inevitably die after blood stops circulating.
Writing in the journal Nature, researchers in the US reported how they sought to examine this further by taking brains from 32 pigs that had been killed in a slaughterhouse. Four hours after their deaths the arteries of the pig brains were hooked up to a sophisticated system dubbed BrainEx, which pumped an oxygenated synthetic blood through the organ. This fluid contained a host of nutrients as well as other substances to tackle processes that lead to cell death, and the circulation was continued for six hours.
At that point, the team found the circulating fluid successfully flowed through blood vessels in the brain, including tiny capillaries, and that the blood vessels were able to dilate in response to a drug, while the brain as a whole consumed oxygen and glucose from the fluid and released carbon dioxide back into it at similar rates to an intact brain.
Unlike pig brains that were left alone for 10 hours after death, the organs that had been hooked up to the BrainEx system for six hours had not decomposed, while their cells and neurons were apparently on a par or even in better condition than for pig brains analysed one hour after death.
What is more, the cells showed certain functions, including the release of various immune-response substances when triggered.After tissueswere removed from the brains and flushed of the BrainEx fluid the researchers found individual neurons were still able to function.
“What we are showing is that the process of cell death is a gradual, stepwise process and that some of those processes can be either postponed, preserved or even reversed,” said Sestan.
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The team said that while the BrainEx fluid was circulating, they monitored the brains to check for any signs of organised electrical activity that might suggest consciousness. “That monitoring didn’t show any kind of organised global electrical activity,” said Dr Stephen Latham, a bioethicist and co-author of the study, adding that the circulating fluid contained substances that would have blocked activity of brain cells.
But, he said, the team had been ready for signs of consciousness. “Had that appeared they would have lowered the temperature of the brain and used anaesthesia to stop that kind of activity,” said Latham, adding that at present there are no ethics committees set up for such an eventuality, and it remained unclear in any case if the technique could ever restore consciousness.
The researchers said it was not clear if the circulating BrainEx fluid was helping to patch up molecular and cellular damage that had already begun, or whether it was simply slowing down such processes, postponing cell death. Latham said the next step would be to see if the system can keep the various cellular functions going for longer. A patent for the system has already been filed.
Experts writing in two articles also in Nature said the research opened up ethical conundrums – not least whether consciousness would have been recorded if the BrainEx fluid had not contained substances to block brain cell activity, and whether other methods were needed to assess consciousness. They also warned the prospect that one day some brain function might be restored after devastating injuries may mean doctors and family members could be less willing for organs to be removed from people for transplant.
Prof Tara Spires-Jones from the University of Edinburgh said the research offered a new way to study the brain.
“A better understanding of brain function is important for understanding what makes us human and will also help us treat devastating diseases of the brain like Alzheimer’s disease,” she said. “However, this study is a long way from preserving human brain function after death as portrayed in the cartoon Futurama where heads were kept alive in a jar. It is instead a temporary preservation of some of the more basic cell functions in the pig brain, not the preservation of thought and personality.”