Thursday, April 18, 2019

Dead pigs and live brain cells--with implications still to be understood

Dramatic scientific announcements get press coverage before they are well (or at all) understood, but that can still be exciting.  Here's some press coverage of an article that was published yesterday in Nature about restoring some cellular activity in the brains of pigs which had been slaughtered and decapitated.  It may eventually have implications for brain injuries, brain death and (hence) deceased organ donation.
(The Nature article and two commentaries published with it are also linked below.)

NY Times:
‘Partly Alive’: Scientists Revive Cells in Brains From Dead Pigs
In research that upends assumptions about brain death, researchers brought some cells back to life — or something like it.

"In a study that raises profound questions about the line between life and death, researchers have restored some cellular activity to brains removed from slaughtered pigs.

"The brains did not regain anything resembling consciousness: There were no signs indicating coordinated electrical signaling, necessary for higher functions like awareness and intelligence.

"But in an experimental treatment, blood vessels in the pigs’ brains began functioning, flowing with a blood substitute, and certain brain cells regained metabolic activity, even responding to drugs. When the researchers tested slices of treated brain tissue, they discovered electrical activity in some neurons."

Washington Post:
Scientists restore some brain cell functions in pigs four hours after death
Ethicists advise caution with research that blurs the line between life and death.

"The researchers are mindful that this is controversial territory with great potential to stoke outrage or, simply, the heebie-jeebies. Such a head-snapping experiment inevitably generates nightmarish scenarios involving live brains in vats, brain transplants, the Zombie Apocalypse, and other mad-scientist story lines (brilliantly crafted, somehow, by neurons firing away inside the skulls of conventionally living human beings).
"The findings also lead to ethical quandaries, some of which are outlined in two commentaries simultaneously published by Nature. The ethicists say this research can blur the line between life and death, and could complicate the protocols for organ donation, which rely on a clear determination of when a person is dead and beyond resuscitation."

Researchers 'reboot' pig brains hours after animals died
Scientists say ability to revive some brain functions will not change definition of death

And here's the article in Nature:
Published: 17 April 2019

Restoration of brain circulation and cellular functions hours post-mortem
Zvonimir Vrselja, Stefano G. Daniele, John Silbereis, Francesca Talpo, Yury M. Morozov, André M. M. Sousa, Brian S. Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur, Zhen W. Zhuang, Zhao Liu, Rafeed Alkawadri, Albert J. Sinusas, Stephen R. Latham, Stephen G. Waxman & Nenad Sestan
Naturevolume 568, pages336–343 (2019) | Download Citation

The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.
Here are two commentaries published in the same issue of Nature:
Part-revived pig brains raise slew of ethical quandaries
Researchers need guidance on animal use and the many issues opened up by a new study on whole-brain restoration, argue Nita A. Farahany, Henry T. Greely and Charles M. Giattino.

Pig experiment challenges assumptions around brain damage in people
The restoration of some structures and cellular functions in pig brains hours after death could intensify debates about when human organs should be removed for transplantation, warn Stuart Youngner and Insoo Hyun.

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