Tuesday, December 10, 2013

KUMC study: Implant allows rats with brain damage to rapidly recover motor skills

KANSAS CITY, Kan. — Scientists at the University of Kansas School of Medicine and Case Western Reserve University have developed a lightweight, battery-powered device that appears capable of repairing damaged pathways in the brain.

The technology holds promise for the millions of individuals suffering from the damage left by stroke or head injuries.

Neurobiologist Randolph J. Nudo, Ph.D., is the senior author of the study, which appears in The Proceedings of the National Academy of Sciences (PNAS).

Nudo says the project represents an important step toward developing devices that can be implanted in the brains of stroke patients, soldiers with traumatic brain injuries and others with abnormal brain function.

Nudo, a professor of molecular and integrative physiology and director of the Landon Center on

Aging at the University of Kansas Medical Center, worked on the design of a brain prosthesis with Pedram Mohseni, Ph.D., an associate professor of electrical engineering and computer science at Case Western Reserve University in Cleveland.

The idea behind the prosthesis, or microdevice, is similar to defibrillators implanted into heart patients. But instead of monitoring the heart, the microdevice monitors neurons firing in the brain. The aim is to restore communication patterns that have become disrupted by injury or disease.

“We’re basically trying to reproduce the process that the brain uses during development, and that it tries to accomplish after injury, but with electronic components that will artificially bridge these areas,” Nudo says.

In order to test the idea, the components were scaled to fit a rat-sized brain. Powered by a simple watch battery, the microdevice was implanted into rats with damaged frontal cortexes.

The microdevice was designed to record signals in one part of the brain and then translate them into electrical impulses that stimulate another part of the brain. Nudo and his colleagues wanted to see if the artificial communication could help the brain-injured rats recover their motor skills.

To determine if recovery had taken place, the rats were tested on their ability to reach for a food pellet. The task required some skill as the rats had to reach through an opening in a Plexiglas chamber.

The results were striking. Without help from the device, rats with brain injuries struggled to reach for and grasp the pellets. When the device was switched on, they were suddenly able to perform the task with ease. In fact, after two weeks of microdevice-delivered brain stimulation,the rats were performing approximately at pre-injury levels.

David Guggenmos, Ph.D., a student in Nudo’s lab at the time of the experiment and first author of the study, captured the before-and-after tests on video. Nudo says he almost could not believe his eyes when Guggenmos hit the play button. “I almost hit the ceiling,” he says. “It was one of the most exciting things I’ve seen since I’ve been in science.”

The next step is to design and build a device for testing on primates, with the eventual goal of taking into clinical trials with humans. If successful, the microdevice could augment — and in some cases replace — rehabilitation therapy, which is often time-consuming and expensive.

“You just implant it, and it basically fixes the brain pathways that are injured,” Nudo says.

The research is supported in part by the United States Department of Defense. Traumatic brain injury is one of the signature injuries of troops wounded in Afghanistan and Iraq. Nudo and Mohseni presented a commercialization plan for the technology at the American Society for Artificial Internal Organs conference in 2012. The plan won first prize at the conference’s first annual Medical Device Entrepreneur's Forum.

“We think this is a game changer,” Nudo says. “There really has not been anything like this.”

The research was funded by the Department of Defense Traumatic Brain Injury-Investigator-Initiated Research Award Program under Awards W81XWH-10-1-0741/0742 and the American Heart Association under Award 09BGIA2280495. The Advanced Platform Technology (APT) Center, a Veterans Affairs Research Center of Excellence affiliated with Case Western Reserve University, supported the fabrication costs for the chip in the microdevice.

Meysam Azin, Ph.D., a former student in Mohseni’s lab; Scott Barbay, Ph.D., a Landon Center senior scientist; Jonathan Mahnken, Ph.D., associate professor of biostatistics in the KU School of Medicine; and Caleb Dunham, a Landon Center research analyst, are co-authors of the PNAS study.