The brain is an organ that needs oxygen to survive, but it's been known that some brain cells can remain active after death. Researchers have also been able to restore limited cellular function in some animals after death. Scientists have now found that some cells in the human brain keep expressing genes after death, and their size increases during this activity. The findings, which used brain samples that were collected during surgical procedures, have been published in Scientific Reports. They may have implications for research that has used post-mortem brain samples.
In this study, the scientists assessed gene expression in brain tissue several times, mimicking the time of death and a post-mortem period. Cells in the brain called glial cells kept expressing genes, and they sprouted large appendages for hours after death.
"That glial cells enlarge after death isn't too surprising given that they are inflammatory and their job is to clean things up after brain injuries like oxygen deprivation or stroke," said corresponding study author Dr. Jeffrey Loeb, the John S. Garvin Professor and head of neurology and rehabilitation at the University of Illinois Chicago College of Medicine.
Loeb noted that for research on brain disorders like Alzheimer's disease, autism, or schizophrenia that relies on brain samples that have been collected post-mortem, there is no accounting for this molecular activity that occurs after death.
"Most studies assume that everything in the brain stops when the heart stops beating, but this is not so," Loeb explained. "Our findings will be needed to interpret research on human brain tissues. We just haven't quantified these changes until now."
The researchers developed a pattern of gene expression in human brain tissue that was fresh, and it did not agree with any data that has been published on brain tissue gene expression, whether it was in individuals who were healthy or patients with neurological disorders like Alzheimer's.
"We decided to run a simulated death experiment by looking at the expression of all human genes, at time points from 0 to 24 hours, from a large block of recently collected brain tissues, which were allowed to sit at room temperature to replicate the postmortem interval," Loeb said.
Loeb is the director of the University of Illinois NeuroRepository, giving the researchers access to a biobank of samples from consenting patients with a variety of neurological disorders or during routine procedures. They studied these samples and found that around 80 percent of the genes they assessed kept expressing at the same levels for about 24 hours after death.
Another group of genes that neurons are known to express and which are involved in memory, thinking, and other human brain activities, quickly broke down in the hours after death. Loeb noted that these genes are a part of some neurological studies.
There was also a third set of genes whose activity ramped up around the same time the brain activity genes were decreasing in activity. This post-mortem pattern reached its peak after about twelve hours. The purpose of this gene expression is unclear; it may be simply incidentally related to the inflammatory response.
"Our findings don't mean that we should throw away human tissue research programs, it just means that researchers need to take into account these genetic and cellular changes, and reduce the post-mortem interval as much as possible to reduce the magnitude of these changes," Loeb said. "The good news from our findings is that we now know which genes and cell types are stable, which degrade, and which increase over time so that results from postmortem brain studies can be better understood."