Researchers at the University of Pittsburgh and UPMC Children’s Hospital of Pittsburgh have discovered a promising new biomarker of “complex” mild to severe childhood traumatic brain injury, or TBI. Unlike a concussion—which usually resolves within weeks—complicated TBI requires at least one overnight stay in the hospital, signaling a more serious injury.
Posted today on Journal of Neurotraumathis study is the first to identify a signature of potentially reversible chemical modifications of DNA, called epigenetic modifications, that may serve as dynamic markers of recovery after injury and guide future precision repair strategies.
This research brings us closer to understanding how children’s brains respond to injury at the molecular level and how these changes relate to real-world functioning. As a neuropsychologist, I look beyond whether a child can return to school or basic independence. Combining disparate cognitive and behavioral data with molecular insights allows us to lay the foundation for personalized care and promote precision rehabilitation in pediatric patients.”
Amery Treble-Barna, Ph.D., senior author, associate professor of physical medicine and rehabilitation, clinical and translational science, and psychology at Pitt School of Medicine
TBI is the leading cause of disability in children, shaped by a complex mix of biological, psychological, and social factors. As leaders in neurotrauma research in both children and adults, Pitt and UPMC have long led innovation in TBI diagnosis and rehabilitation strategies to prevent premature death and reduce disability.
Building on the long legacy of innovation at Pitt’s Safar Center for Resuscitation Research, the new study adds to the growing body of knowledge about TBI biomarkers in children. In their research, the team focused on modifications of brain-derived neurotrophic factor (BDNF) gene because of its role in neuroplasticity, which is the brain’s ability to reorganize and heal itself after injury. Previous studies have linked BDNF levels to recovery outcomes after TBI in adults, but, until now, no group has examined its epigenetic modifications in children.
By focusing on one of the most widely studied types of epigenetic modifications—DNA methylation—the researchers were able to analyze whether BDNF methylation levels could serve as dynamic biomarkers that reflect biological and psychosocial factors that shape recovery, offering a unique molecular lens into pediatric TBI.
The scientists analyzed blood samples from children with no prior history of TBI or neurological disease, collected over several hours, days and months after the children were hospitalized at UPMC Children’s with complicated mild, moderate or severe TBI. Their analysis found that, during the acute recovery period, children with TBI had a different epigenetic profile compared to children with orthopedic injuries: blood samples from children with TBI had significantly less BDNF DNA methylation, with methylation levels stabilizing and reaching those of the control group by 12 months post-injury.
Importantly, the researchers did not observe any correlation between BDNF DNA methylation and severity of TBI were measured with the Glasgow Coma Scale (GCS), a widely used tool to assess consciousness. This adds to a growing body of evidence that the GCS does not represent the full picture of recovery.
“DNA methylation is dynamic and modifiable, meaning it could respond not only to injury but also to interventions such as diet, exercise and therapy,” said lead study author Lacey Heinsberg, Ph.D., RN, a former neurocritical care nurse and now an assistant professor at Pitt’s School of Nursing who focused on genetics and genomics research. “This opens the door for future research on how we might actively improve recovery trajectories for children with TBI.”
The team is now expanding their work to examine genome-wide DNA methylation and link these changes to long-term neurobehavioral outcomes.
This research highlights Pitt’s leadership in epigenetic and neurotrauma research and the unique collaboration between experts in TBI, neuropsychology, nursing and genetics. Children’s Hospital of UPMC Pittsburgh serves as a clinical partner in advancing pediatric neurotrauma care and research.
Explore the full study, related research and expert insights at:
- Genomics of Patient Outcomes HUB | School of Nursing | University of Pittsburgh
- Children’s Hospital Rehabilitation Unit | Children’s UPMC
- Brain Injury Rehabilitation | UPMC – Pittsburgh PA
- Community resources for brain injury patients and their families
- Basic elements of moderate and severe brain damage | HEADS UP | CDC
- Report to Congress: the management of traumatic brain injury in children
Other study authors include Aboli Kesbhat, Bailey Petersen, Ph.D., Lauren Kaseman, Zachary Stec, Nivinthiga Anton, Patrick Kochanek, MD, Daniel Weeks, Ph.D., and Yvette Conley, Ph.D., all of Pitt., and Keith Owen Yeates, Ph.D.
This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (K01HD097030, R01NS135492).
