Driving research and discovery to solve long-term consequences of traumatic brain injury 

The U.S. Department of Defense recently awarded researchers at The Ohio State University $7.7 million in funding to develop a deeper understanding of cellular changes that occur after a traumatic brain injury to ultimately prevent chronic disturbances in the brain and body over time. The team at Ohio State includes principal investigators Jonathan Godbout, PhD, professor of neuroscience and faculty director of the Chronic Brain Injury Program, Kathryn Lenz, PhDassociate professor of psychology, Cole Vonder Haar, PhDassistant professor of neuroscience and Olga Kokiko-Cochran, PhD, assistant professor of neuroscience.patient exam
Traumatic brain injury (TBI) is a leading cause of physical and behavior dysfunction and neurodegenerative disorders in the United States. It creates change on cellular levels in the brain, and many who survive the initial injury go on to face long-term consequences. These consequences include chronic neuroinflammation, autonomic nervous system dysfunction, neuropsychiatric complications and disease.

The Brain Trauma Foundation estimates that 2.5 million Americans sustain TBI annually, making research essential. Currently, there is no known cure for TBI. Learning how these cellular changes are activated during and after an injury and if there is a way to control their responses is critical. Equally important is understanding how stress experienced prior to a brain injury can worsen functional outcomes for people who suffer with TBI.

The funding gives our researchers the ability to take the lead in developing a deeper understanding of these cellular changes to translate the knowledge into breakthrough interventions that prevent chronic disturbances in the brain and body over time.

Jonathan Godbout says since the consequences of TBI continue to occur as time passes, the resulting neuroinflammatory processes persists and can continue to disrupt brain homeostasis. Instability can lead to cognitive, mood and behavior problems that can’t be seen nor detected during testing.

“Think of this continued instability as what is hiding under an iceberg,” Dr. Godbout says. “A patient just doesn’t feel right and if you can’t see it, it can be difficult to diagnose and treat.”

Four investigative projects taking place over the next four years will examine different mechanisms to test and define the contribution of microglia priming to the onset and continuation of brain and behavioral dysfunction after TBI. Microglia are specialized cells in the brain, and once they develop an exaggerated or heightened response, further disruption of brain stability can occur, and neuropsychiatric complications and neurodegenerative diseases can develop.

Dr. Godbout and his team will investigate the role specific immune cells contribute to chronic inflammation and neuronal dysfunction after TBI. Kathryn Lenz will examine how early-life stress-induced microglia priming influences the vulnerability to pediatric TBI. Cole Vonder Haar will assess how primed microglia influence impulsivity after TBI. Olga Kokiko-Cochran will examine the role microglia priming plays in sleep disruption stress after TBI.

This comprehensive collaborative project brings together an interdisciplinary team across the university, including members with expertise in neuroscience, psychology, animal behavior, electrophysiology, and biomedical informatics. The bioinformatics team uses advanced technology to interpret and further complex data generated during research and turn it into leading-edge discoveries. The electrophysiology core performs recordings and analyses of neuron signaling and synaptic function in brain slices. The rodent behavior core performs specialized testing tailored to mice and rats with relevance to human behaviors. This existing infrastructure will aid the researchers in testing their main hypothesis and its validity.

“Each project will meet weekly to monitor scientific progress and inform and also be informed by the other projects,” Dr. Godbout says. “This will allow us to address barriers and resolve challenges early on to advance the development of innovative, personalized health care and a deeper understanding of how infections, stressors and injury add subsequent immune challenges and psychological stress.”

According to Dr. Vonder Haar, these projects strive to not just understand cellular change from brain injury, but to tie that to how neuron activity changes and ultimately affects behavior.

“This translational approach has potential to yield therapeutics to address what patients want: improvements in function,” Dr. Vonder Haar says.

Dr. Kokiko-Cochran adds that brain injury doesn’t occur in isolation and the projects strive to appreciate how recovery from brain injury changes over time.

“This increased understanding of how injury unfolds in the brain over time could decrease complications post-TBI to improve quality of life and longevity,” Dr. Kokiko-Cochran says.

“My hope is that this comprehensive work will give us a window into how and when microglia could be targeted after TBI to help improve symptoms” Dr. Lenz says. “These intervention strategies could be different if you experience an injury during early life versus adulthood, for example, which is why comparing results across our team is so crucial.”

The resulting data will be accessible to the public and augment research started by two impactful programs elevating team science and psychoneuroimmunology at Ohio State, the Chronic Brain Injury Program and the Institute for Behavioral Medicine Research. These programs have a storied history of connecting science and the public and impacting human health in ways unimaginable in years past.