Complex swine brains opening the door for neuroscience

A new study has partially revived cellular function in 32 pig brains, questioning the long-held definition of brain death and opening up new opportunities for restoration of brain function.
calendar icon 20 April 2019
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Published in the international journal, Nature, the study investigated the ability of a complex mammal (pig) brain's ability to recover from 'death'. This work could pave the way for scientists seeking to restore brain function of patients that have suffered heart attacks and other trauma that have caused a loss of normal blood flow to the brain.

The current study used the brains of 32 pigs that had been slaughtered for meat at a nearby food processing plant, meaning the animals were not slaughtered for the purpose of the experiment.

The brains had been 'dead' for hours but when connected to the BrainEx, a network of computer-controlled pumps and filters feeding a 'nourishing solution' to the brain, electrical communication was detected in neurons. This firing of neurons taken from the hippocampus of each treated brain indicates that neural activity is possible even hours after what is defined as brain death.

In an interview with National Geographic, study coauthor and director of the Yale Interdisciplinary Center for Bioethics Stephen Latham says that the aim of the research was never to restore consciousness but was an investigation into the resilience of the human brain. Such experiments are governed by strict ethical regulations and the subjection of any animal to pain is not sanctioned without "a very good motive and the appropriate experiments," says Allen Institute for Brain Science director Christof Koch.

Abstract

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.

References
References
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
(2019) Restoration of brain circulation and cellular functions hours post-mortem. Nature, 568:336–343
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