Seeking Ways to Reverse Nerve Damage at the Microscopic Level

Derron Bishop, associate professor of medical education and assistant director of the Center for Medical Education, played an important role in research that landed him and a team of international scientists the April 2011 cover story on Nature Medicine, which addressed reversible nerve damage at the cellular level.

Bishop and his colleagues sought to pinpoint and label an individual cell among hundreds of thousands of almost identical cells.

“Someone once said, ‘Well that’s like finding a needle in a haystack.’ It’s worse,” says Bishop. “This is like finding a needle in a needle stack.”

For three years, Bishop and medical researchers from Germany and Harvard University searched for that proverbial needle.

“We failed monumentally,” he says. “I had more or less given up on it. For three years, we came up with all kinds of ways. None of them worked.”

Composite of more than 200 microscope images shows the endings of two nerve cells. Actual size is about 1/10th of a human hair.
Then two of Bishop’s German collaborators visited Ball State with a new laser microscope. They had found a way to burn small marks in tissue without burning the top or bottom layer. Together with Bishop, the scientists created a technique of laser-burning a box around a specific part of a cell. They called their innovative technique near infrared branding.

The technique allows scientists to quickly find and view the unaltered cell at a very high resolution using an electron microscope.

The researchers were able to identify and monitor the cellular phenomenon that precedes the death of an axon (part of a nerve cell that conducts impulses), suggesting that inflammatory axon damage might be spontaneously reversible. These findings could eventually help treat problems like multiple sclerosis and spinal cord injuries.
Confocal microscope image of genetically-encoded fluorescence
in the brain of a mouse.
Bishop is using the near infrared branding in his current research on aging to concentrate on individual synapses connecting brain cells.

“A pharmaceutical company is not going to spend three or four years doing the research we did, but now this is out there for the world to use to address, say, a disease model like multiple sclerosis,” Bishop says. “This basic research is central to our National Institutes of Health funding.”

Bishop’s laboratory has itself received a booster shot in the form of a transmission electron microscope. Funded by the National Science Foundation, the nearly half million-dollar electronic tool will enable Bishop and colleagues in biology, chemistry, physiology, and physics to focus on their research (literally and figuratively) with a finer and more powerful lens.

 Derron Bishop with graduate student Kayla Coffin.
Spanning scientific agendas from structural plasticity in the developing nervous system, to unique luminescent thin films for noninvasive biological imaging, to novel photocatalytic solid surface materials for organic decontamination, the transmission electron microscope will enhance Ball State’s research capabilities on campus and far beyond.