Findings on Traumatic Brain Injury Show Path to Diagnosis, Treatment

UCLA researchers found genetic and blood changes follow TBI.

Traumatic brain injuries do more kinds of damage than thought, a pair of University of California Los Angeles researchers have found. That includes changes in leukocytes—a finding that could help diagnosis and treatment of related disorders.

Writing in EBioMedicine, Xia Yang, PhD, (photo, left) and Fernando Gomez-Pinilla, PhD (right) have identified master genes they believe control hundreds of other genes linked to a variety of neurological conditions, behavioral conditions, and illnesses.

These include Alzheimer’s disease, Parkinson’s disease, post-traumatic stress disorder, stroke, attention deficit hyperactivity disorder (ADHD), autism, schizophrenia, and other disorders.

“We believe these master genes are responsible for traumatic brain injury adversely triggering changes in many other genes,” said Yang, a senior study author and UCLA associate professor of integrative biology and physiology.

The duo say genes have the potential to become any of several types of proteins, and that traumatic brain injury can damage these master genes in turn leading to other genes being damaged.

In their study, Gomez-Pinilla, a UCLA professor of neurosurgery and of integrative biology and physiology said they sought to learn how people with brain trauma, including soldiers and footballs players, go on to develop neurological disorders. He is co-senior author of the study.

The study focused on rats who were given concussion-like injuries and then tested on their ability to navigate a maze they had earlier mastered.

It took a group of brain-injured rats 25% longer to complete the task.

The researchers found that when they drew RNA from these injured animals' hippocampi and from their leukocytes there were key alterations.

In all, 268 genes in the hippocampus had been altered and a core group of 1,215 genes in the leukocytes.

Though they weren’t surprised by the changes in the brain cells’ genes, finding the alterations in the leukocytes was a revelation, Yang said. It was not clear what role if any those changes might play in future illnesses or conditions but immediately suggested a possible diagnostic pathway.

The finding suggests that scientists could develop a blood test that by checking for such changes in leukocytes would indicate that an injury was serious. It could also pave the way for new treatment targets for brain disorders. Since more than 100 of the rats’ genes that changed after the brain injury have counterparts in humans that have been linked to neurological and psychiatric conditions, the findings should apply to humans. The scientists plan to conduct studies on people who have survived brain injury to see if they find similar changes.

In addition, the researchers are now studying some of the master genes to determine whether modifying them also causes changes in large numbers of other genes, making them even more promising as therapeutic targets.

A diagnostic test might one day also serve to predict which if any neurological conditions a brain injury patient might develop, such as Alzheimer’s.

Not everyone with a brain injury develops the same disease, but more severe injuries can damage more genes, said Gomez-Pinilla, who is also a member of UCLA’s Brain Injury Research Center.

Their report is entitled “Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders.”