A team of researchers has restored some brain functions in a pig that died 4 hours earlier . The findings challenge pre-existing notions of postmortem brain functionality and open up new possibilities for studying the human brain.
Nenad Sestan, professor of neuroscience, comparative medicine, genetics and psychiatry at Yale School of Medicine in New Haven, USA, and his team have restored circulation and cellular activity in a pig’s brain, postmortem. However, the researchers caution that they did not restore any electrical brain activity or find evidence of consciousness or perception.
The findings contradict the earlier belief that some brain functions are irreversibly lost after death. Additionally, the results of this study could offer scientists a way to study the brain in its intact form. The experiment is detailed in the journal Nature.
Restoring the brain
Mammalian brains, the researchers explain, are highly sensitive to oxygen deprivation , leading to neuronal death and brain damage. The prevailing scientific understanding is that the chain reaction of cellular damage caused by cutting off the oxygen and blood supply is irreversible.
But experts wanted to see how irreparable the damage was . They did so after noticing signs of cell viability in the tissue samples they routinely tested in their lab. They saw these signs several hours after the tissue died. Thus, they developed a system called BrainEx , which mimics the flow of blood at normal body temperature, to test their hypothesis.
In the current study, the researchers acquired 32 pigs from a meatpacking plant and placed them on BrainEx four hours after the pigs had died.
After 6 hours of blood transfusion, the researchers found a reduction in cell death and the return of some synaptic activity between neurons. They preserved the integrity of the neurons, and the scientists found signs that the neuronal, glial and vascular cells were functional.
“The intact brain of a large mammal retains a previously underestimated ability to restore circulation and certain molecular and cellular activities several hours after circulatory arrest,” Sestan explains.
However, the researchers emphasize that they found no evidence of normal electrical activity to indicate complete brain function. “At no point did we observe the type of organized electrical activity associated with perception, consciousness, or consciousness,” the authors clarify. “ Clinically defined, this is not a living brain, but it is a cellularly active brain ,” says Zvonimir Vrselja, co-author of the work.
Clinical significance
Studying the intact mammalian brain has been a challenge that until now seemed insurmountable. “ For the first time, we are able to investigate the large brain in three dimensions , which increases our ability to study complex cellular interactions and connectivity,” says Stefano G. Daniele.
In addition, the BrainEx system could one day allow doctors to reduce brain damage and restore brain function after stroke.
According to Martin Monti, Associate Professor in the Departments of Psychology and Neurosurgery at the University of California, Los Angeles (UCLA), who was not involved in the study: “Death is a process and it takes time, not just seconds or minutes, we knew that.The breakthrough here is that, with the right technology, we may now have more time to regain some molecular, cellular, and microvascular functions before these are fully compromised in the non-human animal model, a perspective that could one day extend the line of potential time for restorative interventions in human tissues. However, this is not to be confused with acts of magic that restore any function to the long-gone favorite hero, which will not happen any time soon, and neither should it be confused with re-infusing cognitive processing, far from it. . Despite the impressive result, no global electrical activity could be detected, not even a remote precursor to the complex interactions necessary for any cognitive function to emerge. “
Regarding the possibility of transferring this advance to the human brain, Monti comments that, “exciting as the results are, the animals remained in a state of complete neuronal silence, thus leaving one of the main criteria for brain death intact.Furthermore, it is also unknown whether this result in the porcine model will ever translate to humans. So for now, the cautious interpretation of this work is that, with this technology, the window to rescue deeply damaged neural tissue from the dying process, in the pig model, could be larger than we thought. It is already a remarkable achievement. “
Referencia: 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. Nature volume 568, pages336–343 (2019). DOI: https://doi.org/10.1038/s41586-019-1099-1
