Rapid Autopsies the Tool in Arizona, Nebraska Quest for Neurons

Editor's Note: This is Part Two of a two-part story on rapid autopsies. Part One reported that University of Nebraska Medical Center scientists are traveling next week to observe rapid-autopsy techniques at a research institute in Arizona.

LINCOLN - Rapid autopsies used to obtain brain tissue for medical research are exceedingly complicated and difficult, but offer fascinating scientific rewards for the effort.

Scientists at the University of Nebraska Medical Center are in the intermediate stages of developing a rapid-autopsy program, so they can stop using aborted fetal tissue in trying to treat Alzheimer's and other diseases. Anti-abortion activists and politicians have put pressure on UNMC to stop using the aborted tissue, and are trying again to ban its use after a legislative attempt failed last year.

Next week UNMC scientists will visit a research institute in Arizona that became a pioneer in rapid-autopsy techniques because of a ban on fetal-tissue research in that state. Arizona's ban has since been ruled unconstitutional, but Sun Health Research Institute's experience continues to be of interest to scientists around the country. The Sun City, Arizona institute's lineup of visitors includes researchers from UNMC Tuesday through Friday, Wayne State University in April, and New York University sometime in the spring.

Rapid autopsies are performed on people who have agreed to donate their brains to science. In the case of Sun Health's around 2,800 donors, they're people who have put stickers on their driver's licenses and medical charts that indicate they're brain donors. They've also informed friends and family so that as soon as they die, someone will call Sun Health's 24-hour autopsy-team hotline.

They're called rapid autopsies for a reason, after all. It turns out that when brain activity ceases and person is clinically dead, many brain cells die off and become useless for research. But, some cells can survive if doctors can extract them within an hour of death. So a team of doctors, nurses, technicians and others must be on call 24 hours a day, 365 days a year -- because people don't always die from 8 a.m. to 5 p.m. on business days.

"You have to have attended to every detail in advance as far as possible," said Joseph Rogers, president of Sun Health.

When brain donors die, they're brought to Sun Health. Doctors remove a 40-gram sample of brain tissue, about half the size of your fist. The procedure is not disfiguring; donors can still have an open-casket funeral.

The sample is immediately plunged into an ice-cold nutrient solutions. Chemicals are then used to disassociate, or dissolve, the tissue sample into its several different component cell types. These cells are then centrifuged -- spun around at extremely high speeds -- so that they clump together in different groups, based on their weight and other properties. Three types of cells are put in fancy test tubes with nutrient solutions that approximate conditions in the living brain, and the test tubes are placed in incubators that keep them at body temperature. The cells attach to the bottoms of the test tubes -- and survive.

"Now we've got for the first time living cells from Alzheimer's patients that we can test," Rogers said. "You can't test drugs on dead tissue. They don't do anything."

There are three cell types Sun Health works with: Neurons, microglia and astrocytes. These are the same kinds of cells UNMC now gets from samples of fetal brain tissue, but would like to obtain from rapid autopsies.

Unfortunately for the UNMC researchers, studying Sun Health's techniques won't mean an instantaneous ability to abandon fetal tissue. "With microglia and astrocytes, it took us six years just to work out the details," Rogers said. "The neurons are still a work in progress."

And there's the problem. UNMC's five reported rapid autopsies have yielded the support, or helper, cells called microglia and astrocytes, but not the all-important "thinking" cells, the neurons. (For more on the roles of these cells, see StatePaper's article, "Gendelman Explains Science Behind Fetal-Tissue Research.")

"We don't get very many nerve cells that are still alive," Rogers said. They're many times more fragile than astrocytes, which Sun Health has managed to keep alive for several months; and microglia, which last for two months.

The neurons can be kept around for one month, but they're not functional like the astrocytes and microglia. The process of separating the neurons from the other cell types amputates the nerve fibers, the all-important connections between neurons that form the basis for how the brain functions.

"We can't get the nerve fibers to re-grow," Rogers said. It's been a major achievement just to keep the neurons alive for short periods of time. "The nerve cells are extremely fragile. But in some ways, they're the prize. It is loss of nerve cells, and the connections between nerve cells, that cause Alzheimer's disease."

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This story originally appeared in Nebraska StatePaper on February 25, 2001.