By Rachael
Rettner, Senior Writer | April 17, 2019 01:00pm ET
In a radical experiment that
has some experts questioning what it means to be "alive," scientists
have restored brain circulation and some cell activity in pigs' brains hours
after the animals died in a slaughterhouse.
The results, though done in
pigs and not humans, challenge the long-held view that, after death, brain
cells undergo sudden and irreversible damage.
Instead, the findings,
published today (April 17) in the journal Nature,
show that the brain of a large mammal "retains a previously
underappreciated capacity for restoration" of circulation and certain
cellular activities hours after death, said study senior author Nenad Sestan, a
professor of neuroscience, comparative medicine, genetics and psychiatry at
Yale School of Medicine in New Haven. [10 Things
You Didn't Know About the Brain]
"The main implication of
this finding is that … cell death in the brain occurs across a longer time
window that we previously thought," Sestan said during a news conference
yesterday. Rather than happening over a course of seconds or minutes after
death, "we are showing that … [it's] a gradual, stepwise process,"
and that in some cases, the cell
death processes can be postponed or even reversed, Sestan said.
Still, the researchers
stressed that they did not observe any kind of activity in the pigs' brains
that would be needed for normal brain function or things like awareness
or consciousness.
"This is not a living brain," Sestan said. "But it is a
cellularly active brain."
The work could provide
scientists with new ways of studying the brain, allowing them to examine
functions in the entire, intact brain in a way that hasn't been possible
before. This in turn could help scientists better understand brain diseases or
the effects of brain
injury, the researchers said.
Although the current study was
done in pigs and not humans, pig brains are larger and more human-like compared
with rodent brains.
"BrainEx"
In the study, the researchers
developed a novel system for studying intact, postmortem brains,
dubbed BrainEx. It's a network of pumps that pipe a synthetic solution — a
substitute for blood — into the brain's arteries at a normal body temperature.
Using BrainEx, the researchers
studied 32 postmortem pig brains that were obtained from a pork-processing
facility (which would have otherwise been discarded). The brains were placed in
the BrainEx system 4 hours after the pigs' death, and were allowed to
"perfuse" with the synthetic blood substitute for 6 hours.
Scientists have developed a
system called BrainEx that preserved and even restored brain cell activity in
pigs' brains after death. Above, images of brain cells with neurons shown in
green, astrocytes (a type of support cell in the brain) in red, and cell nuclei
in blue. After death, neurons and astrocytes undergo cellular disintegration
without any treatment (left), but if brains are placed in the BrainEx system,
these cells are salvaged (right).
Credit: Stefano G. Daniele
& Zvonimir Vrselja; Sestan Laboratory; Yale School of Medicine
During this time, the BrainEx
system not only preserved brain cell structure and reduced cell death, but also
restored some cellular activity. For example, some cells were metabolically
active, meaning they used glucose and oxygen and
produced carbon dioxide. Other cells reacted with an inflammatory response when
stimulated with certain molecules.
In contrast,
"control" brains that were not treated with BrainEx rapidly
decomposed.
"We can see dramatic
differences between the brains we are treating with our technology" and
control brains, Sestan said.
Ethical concerns
Dr. Neel Singhal, an assistant
professor of neurology at the University of California, San Francisco, who
wasn't involved with the study, said the work was "thought
provoking," because of some of the ethical issues raised. For example,
although scientists are a long way from being able to restore brain function in
people with severe brain injuries, if some restoration of brain activity is possible,
"then we would have to change our definition of brain
death," Singhal told Live Science.
The researchers did not see
any signs
of consciousness, nor was this a goal of the research. In fact, the
synthetic blood solution included several chemicals that block neural activity,
the kind of activity that would be needed for consciousness.
What's more, if any type of
organized electrical activity — the kind needed for consciousness — had
appeared, the researchers were prepared to take action to stop that activity by
using anesthesia and lowering brain temperature, said study co-author Stephen
Latham, director of Yale's Interdisciplinary Center for Bioethics. In other
words, terminating the experiment if this happened.
In a commentary published
alongside the study, Nita Farahany, a professor of lawand philosophy at Duke
University, and colleagues called for more guidelines around the ethical issues
raised by the study, which they say "throws into question long-standing
assumptions about what makes an animal ― or a human ― alive."
Such issues include how to
detect consciousness to begin with and how long systems like BrainEx should be
allowed to run.
Future work
Because the study lasted for
only 6 hours, more research is needed to know whether BrainEx can preserve
brains for longer than this time.
In addition, a lot of
questions remain about how similar this model is to the brain environment. The
system does not use real blood, and the brain is not bathed in fluid as it is
inside the skull, Singhal said.
But if the system can be used
in future brain research, this "could lead to a whole new way of studying
the postmortem brain," Andrea Beckel-Mitchener, the team lead at the
National Institutes of Health's BRAIN Initiative, which co-funded the research, said
in a statement. "The new technology opens up opportunities to examine
complex cell and circuit connections and functions that are lost when specimens
are preserved in other ways," Beckel-Mitchener said. The work also could
stimulate research on ways to promote brain recovery after loss of blood flow
to the brain, such as during a heart attack.
Still, the study didn't come
close to being able to revive a brain, pig or human, after death.
"Basically, when the brain loses circulation, it's like a very intricate
building has just [started] crumbing into a million pieces," Singhal said.
The new work suggests that this method "can restore some of the foundation"
but there's still the cathedral of the brain to be built on top of that
foundation, he said.
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