A team of scientists from Yale University detected electrical activity in brain cells from dead pigs. The unexpected results raise questions about what it means for a cell to be dead.

Organs without oxygen do not survive, yet a team of researchers led by Dr Nenad Sestan at Yale University challenged this universal dogma. They studied dead brains from pigs that had been killed in an abattoir, to see whether dead cells can be reactivated when injected with a blood-like substance. The surprising results, published in April 2019, showed that cells could be reactivated and the brain itself was still functional 10 hours after being considered dead.

“When we started this study, we really never imagined we would get to this point,” said Dr Nenad Sestan, neuroscience researcher and one of the authors of the paper published in Nature.

Why Study Dead Brains?

A body without oxygen rapidly fades and dies, thus a brain with no oxygen follows the same path. As soon as brain cells stop receiving oxygen, tissue quickly deteriorates, loses function, and cells die.

However, several studies have shown that brain death does not happen as we once thought. Previous research reported that mitochondria (the powerhouses of the cell) in dead brain cells were still working after the cells were considered dead. Other studies in mammals showed that after one hour without oxygen, cells could still recover if they received a supply of oxygen.

Thus, questions arise. Do brain cells die once there’s no oxygen? Could we recover a cell’s activity by pumping nutrients and oxygen? Dr Nenad Sestan and his team wanted to answer these questions, so they injected oxygen and nutrients into dead brain cells to see if they could be reactivated.

How Were the Brain Cells Brought Back to Life?

The team used a system called BrainEx – a device to pump oxygen into the dead brain. Four hours after collecting the brains, researchers connected them to the device and maintained an oxygen-based fluid circulating for six hours. This way, 10 hours after brain death they could finally look at the cells and understand whether the BrainEx restored some cell function. To get accurate conclusions, scientists compared brains that received the supply from the Brain Ex machine and brains that received a fake supply, known as the control group.

What was discovered?

Dr Sestan’s team was able to restore life in cells that had previously been considered dead, and they understood their results by simply looking at what cells were doing:

“What we can show is that the brain, and that is the cells, are consuming oxygen… and are producing CO2… so it’s a clear sign that these cells are alive,” said Dr Sestan.

The results also showed that the anatomy of the brains that had been connected to the BrainEx system was intact. Even the most sensitive regions kept a functional structure. The arteries and capillaries were working too, and the main cells of the nervous system (known as neurons) were in good shape. A comparison between a normal dead brain and a BrainEx brain can be seen in the figure below (move the grey slider).

 

Finally, after realising that the brain was still highly functional 10 hours after death, the scientists made one last test. They searched for electrical activity, a sign of consciousness.

This approach had ethical implications. Bringing back consciousness means the brain could “feel” pain, so the team was ready to shut down the experiment if they found any sign of resuscitation. However, after testing, they found minor electrical activity, which was not enough for the brain to be conscious or aware. 

Putting it simply, the brain was not alive, yet its cells were not dead either, as Dr Sestan further explained: “At the cellular level, these brains are very close to being alive, but if we consider the life of the brain as the expression of the functionality of the brain, then they’re very far from being alive.”

What Next?

When it comes to learning about the brain, the scientists were stuck with studying either dead brains or simulations of living brains. Until now.

Researchers could now study a close-up version of the living brain by connecting dead brains to the BrainEx system. This novel model to study the brain could unlock new possibilities. Simone Di Giovanni, a professor of neuroscience at Imperial College London, states further that, “This can be something that we could explore in the future to understand cellular and molecular mechanisms of disease.”  

Even though possibilities are ahead, Dr Sestan still wants to understand how long the brain cells could be active while plugged to the BrainEx. After all, cells were functional 10 hours after death, but could they still be active after 15 hours? Research is still needed to understand the threshold. “It is conceivable we are just preventing the inevitable, and the brain won’t be able to recover,” Dr Sestan says. “We just flew a few hundred metres, but can we really fly?”

Featured image: George Tuli

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