Scientists Bring Pig's Brain, Dead 4 Hours, Back to 'Cellular Activity'
The death of brain cells may not be as sudden, or as irreversible, as previously believed.
Four hours after a pig's death, Yale scientists restored circulation and revived cellular activity within the dead animal's brain.
The cells of the brain remained viable six hours later, compared with other brains not preserved using the newly developed process, the researchers reported.
It might sound like Frankenstein, but it isn't, the scientists insist.
Although its cells were kept alive, the brain itself never displayed the sort of organized electrical activity associated with consciousness, said senior researcher Dr. Nenad Sestan. He's a professor of neuroscience at the Yale School of Medicine.
"This is not a living brain, but it is a cellularly active brain," Sestan explained.
So what's the point?
The finding challenges long-held assumptions that brain cells swiftly and irreversibly die off once their blood supply has been cut, the researchers said.
"By doing this, we can possibly come up with better therapies for stroke and other disorders that cause cells in the brain to die," Sestan said.
The same process that preserved the pig's brain also might be used to preserve other organs harvested for donation, added co-researcher Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics.
"It is safe to assume that if this works for preservation of brain cells, it would also work after some tinkering with less sensitive organs in terms of keeping them preserved and keeping their function intact," Latham said.
What it took to revive brain cells
This breakthrough required the development of three unique processes, the researchers said:
- A specially designed blood-like chemical solution tailor-made to preserve endangered brain cells.
- A device that would safely circulate the chemical solution through the brain.
- Surgical procedures to isolate the brain and hook up essential arteries and veins to the circulation device.
Yale researchers named their creation BrainEx, and to test it they picked up freshly severed pig heads from a food processing plant near New Haven, Conn., Latham said.
"The heads with the brains in them were obtained from the plant after the pigs had already been slaughtered for food," Latham said. "No animals were sacrificed for the research."
The goal was not to restore consciousness in the brains, Latham said. The blood substitute contained chemicals that would block neuronal activity, and sedatives were on hand to halt the proceedings if researchers detected any organized electrical activity.
Instead, researchers pursued this study after earlier research indicated that scientists might have been wildly pessimistic about the ability of brain cells to survive after an animal's death, Sestan said.
Cut off from oxygen and a blood supply, the brain's electrical activity and signs of awareness disappear in a matter of seconds, and energy stores are depleted within minutes, the researchers said in background notes. Until now, that has been thought to be part of a swift cascade of brain death that permanently destroys cell function.
Brain death not as simple as thought
But this cascade might not be as overwhelmingly devastating as previously indicated, according to recent research. For example, studies have shown that live cells can be harvested from a brain after death and cultured in a dish, Sestan said.
"This indicates that cells in the postmortem brain have the capacity to be revived," he explained. "If we can do this in a petri dish, can we do this with an intact brain?"
This new study showed 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," Sestan said.
Neural cell integrity was preserved in the pig's brain, and researchers observed some metabolic activity and spontaneous synaptic activity.
While further study might illuminate ways to save the brains of stroke patients, it's not likely that this avenue of research could ever help brain-dead patients being kept alive on life support, Sestan said. It's the difference between saving brain cells versus jump-starting the brain's complex electrical function.
"We found no evidence that these brains have any activity which is associated with perception or consciousness. Activity was completely flat. These brains are really not clinically live brains," Sestan said.
"It's very hard to see at the moment that we can do anything where this could be applied to anybody who is in that state," he concluded.
Breakthrough finding could one day help those with stroke, brain disease
The study is a tremendous breakthrough that upends a lot of pre-existing assumptions in neuroscience, said bioethicist Nita Farahany, a professor and founding director of Duke Science & Society at Duke University.
"Not enough can be said about what an important breakthrough this is for ultimately being able to alleviate the tremendous amount of human suffering that occurs as a result of brain disease," Farahany said.
The study opens the door for "a much better model for studying the human brain, ultimately to have an intact, cellularly functional brain," said Farahany, who co-wrote an editorial accompanying the study.
However, it also leaves researchers "with a gaping gray zone, with almost no guidance of how to proceed ethically," she added.
"We believed there was dead and there was alive, and once something was dead you couldn't bring back the brain," Farahany said.
Ethics committees need to pitch in quickly and help create guidelines under which research like this can be pursued responsibly, she said.
"The researchers here did everything they possibly could to figure out what the ethical path was forward," Farahany added, noting the use of neural blockers and sedatives.
The findings were published April 18 in the journal Nature.
The U.S. Centers for Disease Control and Prevention has more about stroke.
SOURCES: Nenad Sestan, M.D., Ph.D., professor, neuroscience, Yale School of Medicine, New Haven, Conn.; Stephen Latham, J.D., Ph.D., director, Yale Interdisciplinary Center for Bioethics, New Haven, Conn.; Nita Farahany, J.D., professor and founding director, Duke Science & Society, Duke University, Durham, N.C.; April 18, 2019, Nature