Doctors define death based on when the heart stops beating, immediately cutting off blood supply to the brain.  Once this happens, blood no longer circulates to the brain, which means brain function halts almost instantaneously.  Therefore, understanding the stages of brain death to advance the development of intervention prolonging the brain resuscitation window is highly desirable.  Now, a study from researchers at Yale University partially restores circulation and cellular activity in a pig’s brain four hours after its death, a finding challenging long-held assumptions about the timing and irreversible nature of the cessation of some brain functions after death.  The team states many basic cellular functions, once thought to cease seconds or minutes after oxygen and blood flow cease, were observed in the brain of a postmortem pig after being circulated with a specially designed chemical dubbed BrainEx.  The study is published in the journal Nature.

Previous studies show cellular death within the brain is usually considered to be an irreversible process, giving a poor prognosis for resuscitation.  Much research has been performed with a view to lengthening the window of resuscitation. However, researchers’ ability to study an intact, isolated large postmortem brain has been hampered by cell death, clotting of small blood vessels and other toxic processes degrading the tissue following loss of blood flow and oxygen.  The current study develops a technique possessing the capability to keep a large mammalian brain from rapidly decomposing in the hours after death, partially restoring perfusion and capacity, enabling the study of certain functions.

The current study obtains the brains of pigs processed for food production to study how widespread postmortem cellular viability might be in the intact brain. Four hours after the pig’s death the vasculature of the brain was circulated with BrainEx, a solution developed to preserve brain tissue. Results show neural cell integrity was preserved, and certain neuronal, glial, and vascular cell functionality was restored.  Data findings show there was no global electrical activity indicating a lack of higher-order functions, such as awareness or perception.

The lab explains their system pumps BrainEx, a proprietary mixture of protective, stabilizing and contrast agents, into the isolated brain’s main arteries at normal body temperature where it acts as a blood substitute.  They observed brains processed with BrainEx showed reduced cell death, preserved anatomical and cell architecture, restored blood vessel structure and circulatory function, restored glial inflammatory responses, spontaneous neural activity at synapses and active cerebral metabolism, compared to brains perfused with a control solution, which rapidly decomposed.

The team surmises they have developed a tissue support system capable of preserving limited function in an isolated postmortem animal brain four hours after death.  For the future, the researchers state their new technology opens up opportunities to examine complex postmortem brain function and could stimulate research to develop interventions promoting brain recovery after loss of brain blood flow, such as during a heart attack.

Source: Yale University

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