Scientists restore some functions of pig's brain four hours after death

Grant Boone
April 19, 2019

The brains flushed with this solution four hours after death showed reduced cell death; restored blood vessel structure and circulatory function; preserved anatomical and cell architecture, and restored some cellular inflammatory responses, spontaneous neural activity at synapses and active metabolism when compared with rapidly decomposing brains that were flushed with a solution lacking the same necessary ingredients.

The team then obtained 32 pig brains from a food processing facility, meaning no animals had to be killed for the research, and applied the BrainEx technology four hours after death, to model the effects of prolonged brain injury. The scientists also detected electrical activity in some brain cells including those in the hippocampus, a part of the brain central to memory. "Clinically defined, this is not a living brain, but it is a cellularly active brain", study co-author Zvonimir Vrselja, associate researcher in neuroscience.

The immediate benefit of this work will be for scientists studying the brain in diseases like Alzheimer's, as well as helping to find better ways of protecting the brain after traumas such as a stroke or being starved of oxygen at birth.

The research was primarily funded by the National Institutes of Health's (NIH) BRAIN Initiative. The scientists sawed into the skulls and removed the brains. When the researchers tested slices of treated brain tissue, they discovered electrical activity in some neurons. Coauthor Stephen Latham of Yale University says there may be cases where it is ethically justifiable, such as with testing drugs in studies of neurodegenerative diseases, reports Nature.

"Is it possible in the future that more brain function could be restored?" wondered Christine Grady, chief of the Department of Bioethics at the National Institutes of Health Clinical Center.

Still, the study raises a host of bioethical issues, including questions about the very definition of brain death and potential consequences for protocols related to organ donation.

The scientists also found no evidence of global network activity or full-brain function during the experiments.

The latest study suggests a variety of brain functions thought to end within seconds of death - as a result of a lack of blood and oxygen - can actually be restored hours later.

Professor of medical ethics Dominic Wilkinson, who is also a consultant neonatologist in Oxford, said: "Once someone has been diagnosed as "brain dead" there is now no way for that person to ever recover".

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"Could BrainEx ever be used with human brains?".

However, Professor Sestan and his team noticed that small brain tissue samples routinely showed signs of cellular life returning, even when harvested hours after death. "Is there a place at which we would stop doing the research if we got too close to [resurgence of normal brain function]?"

"What we are showing is the process of cell death is a gradual, stepwise process".

The Yale team use pumps, heaters, and bags of artificial blood at body temperature to keep the brains alive.

However, it also leaves researchers "with a gaping gray zone, with nearly no guidance of how to proceed ethically", she added. They pointed out that the experiment did not use live animals.

"It also could stimulate research to develop interventions that promote brain recovery after loss of brain blood flow".

Could the pigs' brains be aware?

As an additional cautionary procedure, the researchers monitored the brains continuously for electrical activity that would indicate global mental operations and were prepared to chill the brains and apply anesthetic if they saw such activity.

Writing in a linked editorial, Nita Farahany, a professor of law and philosophy at Duke University, said that the study "throws into question long-standing assumptions over what makes an animal - or a human - alive".

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