Scientists Restore Partial Function To Dead Pigs' Brains Four Hours After Death

The hippocampal CA3 region of brains left untreated for 10 hours after death (left) or subjected to perfusion with the BrainEx technology (right) shows how many cells BrainEx saves even after four hours. Neurons are stained green, astrocytes red, and cell nuclei blue.  Stefano G. Daniele & Zvonimir Vrselja; Sestan Laboratory; Yale School of Medicine.

The lead up to Easter is an appropriate enough time to be bringing things back from the dead, made perfect by the last season of Game of Thrones. It's presumably a coincidence that the middle of this auspicious period is when a team of scientists announced they have restored partial cellular functioning in the brains of pigs that had been dead for several hours, but it works for us. Today zombie bacon, tomorrow Jon Snow.

Even a brief period without the flow of oxygen-bearing blood in the brain starts a cascade that leads to the death of cells. If the affected areas are large enough, and the interruption long enough, the damage is permanent. However, neuroscientists are divided over how quickly this becomes inevitable.

Professor Nenad Sestan of Yale University reasoned that if the functioning of neurons is to be restored, it would be necessary to supply them with pulsating blood flow at body temperature. Sestan created a support system called BrainEx that pushes a mixture of oxygen carriers and agents that protect and stabilize cells into the brain's main arteries 40-180 times a minute. Thirty-two pigs' brains obtained from a local pork processor were placed inside BrainEx four hours after the pigs were killed and then studied for six hours.

Even four hours after butchering, many individual brain cells were not dead when placed in BrainEx, but the processes that eventually lead to these deaths were well underway. However, Sestan reports in Nature that cell death slowed while the brains were in BrainEx, and some cellular functions returned, including some of the neuron activity in the hippocampus. Blood vessel structure and circulation were also restored, along with the inflammatory response by glial cells that protect and nurture neurons.

It's certainly a long way from pigs, let alone humans, being revived after hours knocking on heaven's door. No evidence of higher-level brain function, such as awareness of the environment, was observed, nor was there activity across the entire brain.

Nevertheless, the work does suggest we may eventually be able to raise some currently defined as dead. More immediately, the work could have many other benefits. "This line of research holds hope for advancing understanding and treatment of brain disorders and could lead to a whole new way of studying the postmortem human brain," said Dr Andrea Beckel-Mitchener of the National Institute of Mental Health in a statement. The rapid deterioration of brains after death has been a major obstacle to neuro-research, and existing preservation methods often cause their own sorts of damage.

Beckel-Mitchener also hopes BrainEx will lead to improved brain recovery after the loss of blood flow from heart attacks or from the deprivation of oxygen to parts of the brain during strokes, as well as better pre-clinical testing of experimental drugs.

For all the benefits, two teams of ethicists wrote accompanying commentaries arguing the work challenges our ideas about when death has occurred. This could move the boundaries of when it is legitimate to use brains in research or take organs for transplantation.

Angiography of a brain being supplied with oxygen by BrainEx from different angles. Vrselja et al./Nature

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