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Scientists Restore Some Brain Function After Death In Animal Experiments (#GotBitcoin?)

The science is still a very long way from having applications in humans, but findings call into question longstanding views of the brain’s limits. Scientists Restore Some Brain Function After Death In Animal Experiments (#GotBitcoin?)

Researchers have found a way to restore some activity to pig brains hours after death, in a series of experiments that medical and legal experts said could reshape science’s understanding of the brain’s limits.

The brains, removed from animals that died in food-processing facilities, were hooked up to a system built by scientists at Yale University that pumped a nutrient-rich fluid through the organ for several hours. Afterward the researchers, who described their findings in the journal Nature, were able to coax cells to fire a type of electrical signal that underpins all brain activity.

Although the team didn’t observe widespread activity between brain regions—a prerequisite for high-level functions like perception, pain and consciousness—the findings still call into question longstanding views of the brain as a fragile organ that deteriorates rapidly and irreparably once it stops getting oxygen, neuroscientists said.

“It blew me away. It was so surprising and so against conventional wisdom that cells could survive or revive after such a long time,” said Hank Greely, a Stanford University law professor and president of the International Neuroethics Society who wasn’t involved in the research. “Assuming always that this work is replicated, I think it’s going to force us to think harder about how we declare somebody dead or not.”

The science is still a very long way from having applications in human brains, and the findings in no way suggest the brain was alive, the research team and other scientists stressed.

“This is not a living brain, but it is a cellularly active brain,” said Yale neuroscientist Nenad Sestan, who led the study.

Still, the results could open up new avenues of study into brain function and how drugs affect it, potentially improving drug development for conditions like dementia or stroke that have for decades stumped the pharmaceutical industry, brain experts said. It also could have future implications for organ donation, forcing the medical community to re-evaluate when it’s appropriate to take organs for transplants, experts said.

“It’s a technological tour de force,” said Christof Koch, a neuroscientist and the president of the Allen Institute for Brain Science, who wasn’t involved in the study.

Traditionally, researchers have used single brain cells—known as neurons—or pieces of tissue to probe the workings of the brain, giving them useful, but limited, insights into how the organ functions.

For this study, the Yale team took intact pig brains four hours after death, and placed them inside a spherical plastic container where each was connected via its blood vessels to a custom-built computerized system of pumps, filters and temperature regulators.

Pig brains more closely resemble human brains than those of mice or rats, which are widely used in neuroscience research.

The system, which the researchers dubbed BrainEx, in essence performs the job of the kidneys, lungs and heart, pumping a special blood-like fluid into the brain with the same rhythm the heart does. In total, they exposed 32 brains to the solution for six hours.

The bright-red solution contains nutrients and chemicals that feed and oxygenate the organ and protect against inflammation, while simultaneously allowing the researchers to image it with ultrasound. It also contained synaptic-activity blockers—molecules that prevent communication between neurons—to prevent brain activity that could result in awareness or brain damage during the experiment, the researchers said.

The team then sliced the brains into thin slivers of tissue that allow researchers to probe neuronal activity in a controlled way. A mainstay of neuroscience, brain slices have been used for decades to record neurons from rodents and primates, including humans.

They focused on the hippocampus, a seahorse-shaped structure important for learning and memory, because its cells are “especially vulnerable” to stress, like oxygen loss, and they’re also iconic in neuroscience research because of their role in memory formation, said Dr. Sestan.

Preliminary experiments some years ago showed that the team’s custom fluid preserved the structure of these cells, known as CA1 and CA3 neurons. “We were utterly shocked. I cried,” recalls Dr. Sestan.

The next step was to see if they were functional.

After washing away the synaptic-activity blockers, the team used tiny zaps of electricity to coax neurons in hippocampal brain slices to fire so-called action potentials, electrical signals that are the building blocks of brain activity.

Brain experts described those results as masterful, but only a baby step toward restoring full brain function following massive injuries like stroke.

“Even though we can restore certain very basic, primitive cell functions, to be able to repair that damage seems like a gargantuan task,” said Neel Singhal, a University of California, San Francisco neurologist who wasn’t involved in the work. “It’s like the building has crumbled, and they’ve just started to rebuild a couple of layers of the foundation.”

In separate experiments, the Yale researchers also tested a drug known to increase blood flow. The brains’ vascular systems responded normally to the drug, suggesting that the BrainEx platform could be used to vet medications in the future and test interventions for stroke, the researchers and other scientists said.

The experiment also included 34 control brains that didn’t get the special fluid, some of which showed widespread cell death, plus blood-vessel collapse.

The Yale team designed the fluid in collaboration with Souderton, Pa.-based HbO2 Therapeutics LLC, which manufactures oxygen-carrying solutions that mimic blood for organ-transplant applications. The collaboration was unpaid, but the company has rights of first refusal to commercialize the technology, according to HbO2 Chief Executive Zaf Zafirelis.

What kinds of neural experiments come next will require careful considerations about what is ethically acceptable, especially if and when the time comes to test human brains, according to scientists and bioethicists.

There are “very clear rules” about experiments scientists can and can’t do on living humans, but “once a human dies and their tissue is in a lab, there are many fewer restrictions,” said Christine Grady, chief of bioethics at the Clinical Center of the National Institutes of Health, which funded the project. “Whether or not there would need to be new rules” is something ethicists are already thinking about, she added.

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