Stefano G. Daniele & Zvonimir Vrselja; Sestan Laboratory; Yale School of Medicine
Stefano G. Daniele & Zvonimir Vrselja; Sestan Laboratory; Yale School of Medicine

The oinking dead - scientists partially restore brain function in dead pigs

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Researchers in the US and Italy have created a system that restored some function in brains of pigs, four hours after they were killed. Through a system that mimics blood flow, the scientists ran experiments on the brains of 32 decapitated pigs and saw a reduction in cell death and the restoration of some functions like synaptic activity - challenging a long-held perception that mammal brains are damaged beyond repair once our hearts stop. Although there was no full brain activity or function, the study raises questions around possible implications for organ transplants, as well as ethical quandaries on animal use, independent commentators write.

Journal/conference: Nature

Link to research (DOI): 10.1038/s41586-019-1099-1

Organisation/s: Yale School of Medicine, USA

Funder: This work was supported by the NIH BRAIN Initiative MH117064, NIH shared instrument grant OD021845, which funded purchase of the microSPECT/CT scanner, and NIH/NIGMS Medical Scientist Training Grant T32GM007205.

Media Release

From: Springer Nature

Neuroscience: Restoring cellular functions in the pig brain after death 

A system that can restore brain circulation and some cellular functions in a pig brain hours after death is reported in this week’s Nature. However, there was no evidence for global electrical brain activity associated with awareness, perception or other higher-order brain functions. This approach may offer a platform for studying the intact brain, but requires further testing before broader applications can be explored.

Mammalian brains are very sensitive to decreased oxygen levels; short periods of interrupted blood flow lead to rapid depletion of oxygen and energy stores, which is thought to cause neuronal death and irreparable brain damage. Some studies have questioned whether this cascade of damaging events is inevitable within a short period after blood-flow disruption.

Nenad Sestan and colleagues postulate that certain cellular brain activities may have the capacity to be partially restored, even a few hours after death. They tested this theory by developing BrainEx, a system designed to mimic pulsating blood flow (perfusion) at normal body temperature (37 degrees Celsius). In this study, 32 pig brains, obtained from food-processing facilities, were placed in this system four hours after death. During a six-hour perfusion period, the authors observed a reduction in cell death and evidence for the restoration of some cellular functions, including synaptic activity. However, there was no evidence of global network activity or full-brain function during the experiments.

The findings indicate that the brain possesses a greater capacity for cellular restoration than was previously appreciated, and that deterioration after cessation of blood flow may be a protracted rather than rapid process. Whether restoration of full, normal brain function might be possible with this system remains unclear. The authors clarify that this effect is not evident in their current study, and further experiments with longer perfusion periods would be needed before broader applications of this system could be considered.

Two related Comment pieces in this week’s Nature consider the implications of research in this area. The BrainEx study could intensify debates about human organ transplantation, argue Stuart Youngner and Insoo Hyun in one Comment. “As the science of brain resuscitation progresses, some efforts to save or restore people’s brains might seem increasingly reasonable ― and some decisions to forego such attempts in favour of procuring organs for transplantation might seem less so,” they write.

In a second Comment, Nita Farahany and colleagues point out that the possibilities opened up by the study highlight “potential limitations in the current regulations for animals used in research”. They call for guidelines to help researchers navigate the host of ethical dilemmas raised by the study, which “throws into question long-standing assumptions about what makes an animal ― or a human ― alive.”

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