PITTSBURGH, – Researchers at the University of Pittsburgh and UPMC Children's Hospital of Pittsburgh discovered a promising new biomarker of "complicated" mild- to severe-pediatric traumatic brain injury, or TBI. Unlike a concussion—which usually resolves within weeks—complicated TBI requires at least an overnight hospital stay, signaling a more serious injury.
Published today in the Journal of Neurotrauma, this study is first to identify a signature of potentially reversible chemical modifications of DNA, called epigenetic modifications, that may serve as dynamic indicators of post-injury recovery and guide future precision rehabilitation strategies.
"This research brings us closer to understanding how children's brains respond to injury at the molecular level and how those changes relate to real-world functioning," said senior author Amery Treble-Barna, Ph.D., associate professor of physical medicine and rehabilitation , clinical & translational science, and psychology at Pitt School of Medicine. "As a neuropsychologist, I look beyond whether a child can return to school or basic independence. Combining nuanced cognitive and behavioral data with molecular insights allows us to lay the groundwork for personalized care and advance precision rehabilitation in pediatric patients."
TBI is a 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 driven innovation in TBI diagnostics and recovery strategies to prevent premature death and reduce disability.
Building on the decades-long legacy of innovation at Pitt's Safar Center for Resuscitation Research , the new study adds to the growing knowledge about TBI biomarkers in children. In their research, the team focused on modifications of the brain-derived neurotrophic factor (BDNF) gene because of its role in neuroplasticity, which is the brain's ability to reorganize and heal after injury. Previous studies link BDNF levels to recovery outcomes after TBI in adults, but, until now, no group has looked at its epigenetic modifications in children.
By focusing on one of the most widely studied types of epigenetic modifications—DNA methylation—researchers were able to analyze whether BDNF methylation levels could serve as dynamic biomarkers that reflect both biological and psychosocial factors shaping recovery, offering a unique molecular lens into pediatric TBI.
Scientists analyzed blood samples of children with no prior history of TBI or neurological conditions, collected over several hours, days and months after the children had been 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 orthopaedic 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 after the injury.
Importantly, researchers did not observe any correlations between BDNF DNA methylation and TBI severity measured by the Glasgow Coma Scale (GCS), a widely used tool for assessing consciousness. This adds to a growing body of evidence arguing that the GCS does not represent the full picture of recovery.
"DNA methylation is dynamic and modifiable, which means it could respond not only to injury but also to interventions like diet, exercise and therapy," said lead author of the study Lacey Heinsberg, Ph.D., R.N., formerly a neurocritical care nurse and now assistant professor at Pitt's School of Nursing focused on genetics and genomics research. "This opens the door to future research on how we might actively improve recovery trajectories for kids with TBI."
The team is now expanding their work to examine DNA methylation across the entire genome and to 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. UPMC Children's Hospital of 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 Inpatient Rehabilitation Unit | UPMC Children's
- Brain Injury Rehabilitation | UPMC - Pittsburgh PA
- Community Resources for Brain Injury Patients and Their Families
- Moderate and Severe Brain Injury Basics | HEADS UP | CDC
- Report to Congress : the management of traumatic brain injury in children
Other authors of the research are Aboli Kesbhat, Bailey Petersen, Ph.D., Lauren Kaseman, Zachary Stec, Nivinthiga Anton, Patrick Kochanek, M.D., Daniel Weeks, Ph.D., and Yvette Conley, Ph.D., all of Pitt., and Keith Owen Yeates, Ph.D., of the University of Calgary, Canada.
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).
