A team of researchers has restored some brain functions in a pig that died 4 hours earlier. The findings challenge pre-existing notions of postmortem brain functionality and open up new possibilities for studying the human brain.

Nenad Sestan, who is a professor of neuroscience, comparative medicine, genetics, and psychiatry at the Yale School of Medicine in New Haven, CT, and his team have restored circulation and cellular activity in a pig's brain, postmortem. However, the researchers caution, they did not restore any electrical brain activity, nor did they find any evidence of awareness or perception.

The findings contradict the previous belief that some brain functions are irreversibly lost after death. Furthermore, the results of this study could offer scientists a way of studying the brain in its intact form. Sestan and his colleagues detail their experiment in the journal Nature.

Restoring a 'cellularly active brain'

Mammalian brains, explain the researchers, are very sensitive to oxygen deprivation, which leads to neuronal death and brain damage. The predominant scientific understanding is that the chain reaction of cellular damage that oxygen and blood supply cut-off triggers are irreversible. But Sestan and colleagues questioned the idea that such damage is irreparable. They did so after noticing signs of cellular viability in the tissue samples that they routinely analyzed in their lab. They saw these signs several hours after tissue death. Sestan and team developed a system called BrainEx, which mimics blood flow at normal body temperature, to test their hypothesis.

In the current study, the researchers acquired 32 pigs from a meatpacking plant and placed them on BrainEx 4 hours after the pigs had died. After 6 hours of blood transfusion on BrainEx, the researchers found reduced cell death and the return of some synaptic activity between neurons. They preserved the integrity of neurons, and the scientists found signs that neuronal, glial, and vascular cells were functional.

"The intact brain of a large mammal retains a previously underappreciated capacity for restoration of circulation and certain molecular and cellular activities multiple hours after circulatory arrest," reports Sestan. However, the researchers emphasize that they found no evidence of normal electrical activity that would indicate full brain function. "At no point did we observe the kind of organized electrical activity associated with perception, awareness, or consciousness," reports co-first author Zvonimir Vrselja, "Clinically defined, this is not a living brain, but it is a cellularly active brain."

Clinical significance and ethical concerns

The researchers explain the significance of their findings. They say that studying the intact mammalian brain has been a challenge that has seemed insurmountable so far. This challenge has stopped researchers from being able to study the origins of certain brain disorders, as well as the connectivity between neurons.

"Previously, we have only been able to study cells in the large mammalian brain under static or largely two-dimensional conditions, utilizing small tissue samples outside of their native environment," explains study co-first author Stefano G. Daniele.

"For the first time, we are able to investigate the large brain in three dimensions, which increases our ability to study complex cellular interactions and connectivity."

—Stefano G. Daniele

Furthermore, the BrainEx system may one day allow doctors to reduce brain damage and restore brain function after stroke.

In a linked editorial, some researchers have raised ethical concerns about the study. Nita Farahany and colleagues, for instance, note that the avenues that the research opens emphasize "potential limitations in the current regulations for animals used in research." The study "throws into question long-standing assumptions about what makes an animal—or a human—alive," continue Farahany and colleagues.

"Restoration of consciousness was never a goal of this research," says study co-author Stephen Latham, who is the director of the Interdisciplinary Center for Bioethics at Yale. "The researchers were prepared to intervene with the use of anesthetics and temperature-reduction to stop organized, global electrical activity if it were to emerge. Everyone agreed in advance that experiments involving revived global activity couldn't go forward without clear ethical standards and institutional oversight mechanisms."