Blood proteins associated with persistent symptoms after brain injury

Researchers looked for markers of mild traumatic brain injury in the blood of military veterans who’d experienced combat. SDI Productions / E+ via Getty Images

More than a million people in the U.S. experience a mild traumatic brain injury (mTBI), or concussion, every year. Causes include falls, motor vehicle accidents, sports injuries, and violence. In most cases, symptoms associated with these injuries go away over a few weeks to months.

But in some people, they persist. In a condition called post-concussive syndrome, people live with chronic symptoms including headaches, balance problems, fatigue, and cognitive issues. Some also develop post-traumatic stress disorder (PTSD), depression, or other mental health problems after an mTBI.

Researchers want to better understand why some people’s brains don’t heal after mTBI. They also hope to identify biomarkers—substances that can be measured in the blood or other bodily fluids—that can help predict who will experience long-term problems after a brain injury.

A research team led by Dr. Jessica Gill from NIH’s National Institute of Nursing Research (NINR) examined possible biomarkers of mTBI in a study of almost 200 military veterans who had experienced combat in the early 2000s. They measured levels of proteins circulating freely in the blood as well as those in exosomes, tiny sacs released by cells that carry proteins through the bloodstream to other parts of the body.

The researchers tested for neurofilament light chain (NfL), a protein that is released when the ends of nerve cells in the brain become damaged. Recent studies have suggested the potential of NfL as a general biomarker of damage to the brain’s neurons. The team also measured levels of four other proteins associated with chronic inflammation. Chronic inflammation may prevent blood vessels in the brain from healing after an injury.

The scientists examined levels of these potential biomarkers among veterans who had experienced three or more mTBIs in their lifetime, one to two mTBIs, and no brain injuries. They also compared levels in those who reported long-term symptoms after mTBI with those who did not. The results were published on June 9, 2020, in Neurology.

Study participants with more brain injuries over their lifetime were more likely to have higher levels of NfL either circulating freely in the blood or bound up in exosomes.

The veterans who reported more symptoms of post-concussive syndrome, PTSD, or depression were also more likely to have higher levels of blood and exosomal NfL. Several of the biomarkers of inflammation showed associations with some long-term symptoms after mTBI as well.

“This study brings us closer to identifying biomarkers to predict risk for PTSD, depression, and similar conditions in military personnel and others who have experienced a traumatic brain injury,” Gill says.

More research is needed to test whether NfL and other biomarkers can be used to accurately predict which people with mTBI will have difficulty healing after injury.