A First Look Inside Traumatic Brain Injury
An estimated 5.3 million Americans are living with a disability related to traumatic brain injury (TBI), and annually, nearly one million Americans are treated and released from emergency rooms as a result of TBI. Even with such high rates of injury, TBI’s impact on the brain is difficult to understand—but researchers at the University of Pittsburgh are looking to change that.
Xinyan (Tracy) Cui, professor of bioengineering at the Swanson School of Engineering, and Amy Wagner, a neurorehabilitation physician and neuroscientist in the department of physical medicine and rehabilitation, received a 5-year, $2.65 million R01 grant from the National Institutes of Health (NIH) for their project “Investigation of Cognitive and Affective Deficits Post TBI Using Multimodal Flexible Neural Probes.”
“With this grant, we want to understand the brain’s neurochemistry after TBI and look at two neurotransmitters: dopamine, which is known to relate to some post-TBI symptoms, and glutamate, an excitatory neurotransmitter that has been found to increase after a traumatic brain injury,” Cui said. “We want to make a tool that can measure both of these neurotransmitters while specifically looking at their concentration in the striatum region of the brain.”
Traumatic brain injury can be mild, moderate, or severe, and is frequently caused by car accidents, falls, sports, or explosions. TBI can cause cognitive or emotional deficits such as memory loss and depression - while dopamine stimulants have proven effective in treating these deficits, the reason why this treatment works is still unknown.
Neurotransmitters such as dopamine and glutamate allow neurons to communicate with each other throughout the body. To understand how clinicians can better treat TBI and its symptoms, Cui's first aim in this project is to develop a multimodal microelectrode array (MEA) tool that measures developing neurotransmitters.
“Currently, there is no tool available to measure neurotransmitters as they develop,” Cui said. “We want to develop such a tool, which will allow us to measure the electrical activities of the neurons and neurotransmitters in the same region simultaneously to help us understand neural transmission and how the neurotransmitters change as the injury evolves.”
MEAs contain multiple microelectrodes that monitor neural signals in the brain, and serve as neural interfaces that connect neurons to electronic circuitry. Once their MEA is developed, the team will then correlate the findings with actual behavior outcome post-TBI and observe how the neurotransmitters relate to different behavior deficits.
“We are using an engineering approach to develop previously unattainable tools that will help neuroscientists better understand neuroscience and also help doctors understand and come up with new treatments,” Cui said.
Overcoming Challenges in Studying TBI
Most existing tools that monitor neurotransmitters fail after a short time period, lasting from just a few hours to about a day, and currently, there’s no tool that can measure both neural activity and neurotransmitters in the striatum for an extended period of time. Cui’s project aims to combat this by developing a longer-lasting tool that will be able to withstand deterioration for three weeks inside the brain.
“We have spent a great deal of time improving the sensitivity and stability of the sensor while trying to understand how the in-vivo environment affects the sensor, damages it or causes it to be sensitive,” Cui said. “We’re now taking some of those results from past research and applying them to our new tool to improve sensor longevity.”
Another challenge in studying TBI is the fact that the injury shrinks and swells over time, which Cui’s team is adapting to by developing a MEA that can adapt to the changing injury.
“A specific challenge with TBI is that as the injury occurs, it's a mechanical impact, and then as the injury develops, there'll be a lot of swelling of the tissue, so a stiff device is not going to accommodate that kind of swelling and shrinkage,” Cui said. “Our device is very flexible so that it can basically maintain its electrical connection and integrity during the deformation of the tissue.”
The project will also begin at a pivotal moment in the world of neuroscience research—the BRAIN initiative, a key program supporting neuroscience research in the United States, faced a 40% cut in funding this fiscal year, with many researchers uncertain about the likelihood of future projects receiving funding.
“I feel especially fortunate that we got this grant since the NIH is cutting funding dramatically,” Cui said. “I hope that people can realize this type of research is important and that we should have more funding coming into any kind of medical health related research.”
Depending on the severity of the injury, those with TBI may face health problems that last just a few days or for the rest of their lives. Outcomes from this project will have broad implications from both design and scientific standpoints, and Cui hopes that her work will ultimately help create more personalized treatments for patients with an array of neurological conditions.
“From the scientific outcome perspective, we will have a better understanding of the mechanisms behind cognitive and emotional deficit post-TBI, so we will be able to have a more customized drug treatment to treat our patients.” Cui said. “And along with TBI, the tool that we develop can be used for a variety of neuroscience research, including depression, schizophrenia, and drug addiction.”