A stroke is like a meteorite impact. There’s a central “core of death” surrounded by silenced neural networks. So far, no one has figured out a way to turn those neurons back on. But by adding adult stem cells to a "brain in a dish" comprised of rat neurons, researchers at the University of Florida could find a way to reboot the brain -- essentially waking up quiet circuits and regenerating the core.
“We take normal neurons, simulate a stroke event, and implant adult stem cells,” said Thomas DeMarse, a research scientist at the University of Florida who is working on the transplant model with assistant professor of biomedical engineering Brandi Ormerod and PhD student Crystal Stephens.
The brain in the dish, or as the scientists prefer to call it, the "“biologically relevant neural model,” is a computer chip with an array of 60 microelectrodes that measure the action potential of neurons grown on top. The microelectrode array, or MEA, records the brain cell signals so the scientists can analyze them.
“The beauty of the MEA is that it doesn’t just tell you the activity of one neuron, it tells you the activity of hundreds at the same time,” DeMarse said. Using MEAs is not new -- DeMarse used one in 2004 to show that brain cells could be used to control a flight simulator -- but adding adult stem cells to the mix in vitro, that is, in an experiment outside the brain, is the new part.
First, they put cells from an embryonic rat brain in the dish. Those neurons began firing and gradually started “talking” to one another. After about a month, the cells generated stable activity patterns, bursting in unison.
At that point the scientists added neural progenitors -- adult stem cells -- to the network in the dish, which hadn’t been done before. The adult stem cells were harvested from rats and were tagged with green fluorescent proteins so they could be distinguished from the original cells in the dish. Neural progenitors are a promising strategy because they can only make brain cells and aren’t going to turn into eyeballs or toenails, Ormerod said.
“After we got the stem cells in, one of the things we wanted to know is, ‘Are they functionally integrating into the network?’” DeMarse said. “One of the first things we saw was a dramatic change in the pattern of activity.” The co-culture generated super bursts of activity, which is usually only found in a developing mammalian brain.
“If you rebuild an area [of the brain], you somehow have to get it to talk to the surrounding areas," Ormerod said. The adult stem cells might actually facilitate the communication between existing brain cells and new ones, enabling doctors to one day reboot the silenced cells of a brain. The researchers recently submitted their findings to the Journal of Neuroscience.
Edward Keefer is chief neuroscientist at Plexon, a Dallas-based company that manufactures neurophysiology equipment including an array containing 4,096 electrodes. He is familiar with DeMarse and Ormerod’s current research.
The scientists are using the system to ask questions about precisely what happens when new stem cells are added. “This in-vitro system -- working outside the brain, but in a culture dish -- is an attempt to explore those types of questions,” Keefer said. “I think it can make a valuable contribution.”
The answers could help determine just how many cells will be needed to restore brain function, he continued. “It’s an experiment in progress.”