Scientists restore partial brain function after death

Circulation and cell activity was restored in a pig's brain four hours after his death, a discovery that challenges conventional wisdom about the timing and irreversible nature of the cessation of certain brain functions after death , Yale scientists reported April 17 in the journal Nature.

The brain of a post mortem pig from a meat packing plant has been isolated and distributed with a specially designed chemical solution. Scientists report that many basic cellular functions, once supposed to stop a few seconds or minutes after oxygen and blood flow have stopped, have been observed.

"The intact brain of a large mammal retains a capacity for restoring circulation and certain molecular and cellular activities that had been underestimated several hours after a circulatory arrest," said lead author Nenad Sestan. , professor of neuroscience, comparative medicine, genetics and psychiatry.

However, the researchers also pointed out that the treated brain had no recognizable overall electrical signal associated with normal brain function.

"We have not at any time observed the kind of organized electrical activity associated with perception, consciousness or consciousness," said co-lead author Zvonimir Vrselja, associate researcher in neuroscience. "Clinically defined, it's not a living brain, but it's an active brain on a cellular level."

Cell death in the brain is generally considered a rapid and irreversible process. Cut off from oxygen and blood supply, the electrical activity of the brain and the signs of consciousness disappear in seconds, while energy reserves are exhausted in minutes. According to current knowledge, a cascade of wounding and deadly molecules is then activated, resulting in generalized and irreversible degeneration.

However, researchers at the Sestan lab, whose research focuses on brain development and evolution, have found that the small tissue samples they worked with consistently had evidence of cell viability, even when the tissue was taken several hours after death. Intrigued, they got the brains of processed pigs for food production in order to study the extent of this post mortem viability in the intact brain. Four hours after the pig died, they connected the cerebrovascular system to circulate a specially formulated solution to develop brain tissue, using a system called BrainEx. They discovered that the integrity of neuronal cells was preserved and that some functional neuronal, glial and vascular cells were restored.

The new system can help solve a thorny problem – the inability to apply certain techniques to study the structure and function of the large intact mammalian brain – which prevents rigorous investigation of topics such as the roots of brain disorders, as well as neuronal connectivity, both for health and abnormal conditions.

"Previously, we could only study cells in the brains of large mammals under static or largely two-dimensional conditions using small tissue samples outside of their original environment," said the co-ordinator. – first author, Stefano G. Daniele, MD / Ph. RE. candidate. "For the first time, we are able to study the big brain in three dimensions, which increases our ability to study complex cellular interactions and connectivity."

Although there is no immediate clinical application, the new research platform may one day help physicians find ways to help save brain function in patients. have had a stroke, or to test the effectiveness of new treatments aimed at cellular recovery after injury, say the authors.

The research was primarily funded by the BRAIN initiative of the National Institutes of Health (NIH).

"This line of research offers hope for a better understanding and better treatment of brain disorders and could lead to a whole new way to study the post-mortem human brain," said Andrea Beckel-Mitchener, head of functional neurogenomics at the National Institute of Mental Health of NIH, which co-funded the research.

The researchers said it was not clear if this approach could be applied to a recently deceased human brain. The chemical solution used is devoid of many components present in human blood, such as the immune system and other blood cells, which significantly differentiates the experimental system from normal living conditions. However, the researcher pointed out that any future studies involving human tissue or a possible resumption of global electrical activity in post-mortem animal tissues should be performed under strict ethical control.

"The restoration of consciousness has never been an objective of this research," said co-author Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. "The researchers were ready to intervene with the use of anesthetics and a reduction in temperature to end the organized global electrical activity, if it were to occur. Everyone agreed in advance that experiences involving renewed global activity could not take place without clear ethical standards and institutional oversight mechanisms. "

Christine Grady, Head of the Department of Bioethics at the NIH Clinical Center, said it was ethically imperative to use the tools developed by the Brain Initiative to solve the mysteries of lesions and diseases of the brain. brain.

"It is also our duty to work with researchers to manage thoughtfully and proactively any potential ethical issues they may encounter when opening new frontiers in the field of brain science," he said. she declared.

Publication: Zvonimir Vrselja, et al., "Restoration of the cerebral circulation and cellular functions after autopsy", Nature, volume 568, pages 336-343 (2019).