This Protein Predicts a Brain’s Future After Traumatic Injury

Neil Graham sees a lot of head injuries: “Car accidents, violence, assault, gunshots, stabbing—the works, really,” says Graham, a neurologist from Imperial College London who practices at St. Mary’s Hospital nearby.

Doctors stop the bleeding, they relieve any pressure building inside the skull, maybe they’ll put the patient into a coma to keep the brain from overworking when it needs to relax and heal. Imaging can also help—to an extent. CT scans or MRIs pinpoint bruising or specks of hemorrhage in gray matter, the brain’s outer layer where neurons do most of their processing. But a clean scan isn’t a clean bill of health. Trauma to axons—a neuron’s root-like fibers that extend toward other neurons—often appears only in the deeper white matter, sometimes eluding simple scans.

Axonal damage is a big deal. Cognition and motor function tank when neurons can’t exchange messages. And when white matter absorbs a blow, the fallout not only can linger, it can worsen, causing severe problems for thinking or movement. But doctors don’t always know about that damage. It’s then hard to give survivors assurances about the future. “The families and the patients are asking us early on, ‘Well what’s it going to look like in six months or a year? When can I get back to work?’” says David Sharp, a professor of neurology at Imperial College London who also practices at St. Mary’s.

Sharp and Graham think they can find the answer in proteins, or biomarkers, carried in a person’s blood. They teamed up with trauma experts across Europe for a study that followed nearly 200 patients with head injuries for one year. The researchers pored over brain scans, plasma analyses, and white matter fluid samples, tracking how five biomarkers correlate with an injury’s severity—and the person’s recovery. In results published in September in Science Translational Medicine, they focused on one protein in particular: neurofilament light (NfL). NfL levels rise for weeks after an injury and can stay high a year later.

Plasma NfL won’t tell you where axonal damage is, but it’s an easier way of measuring damage—and tracking it long-term—compared to advanced MRI techniques.

“Brain injury, you think of it as a single event: Someone has an injury and that’s it, they recover or they don’t,” says Richard Sylvester, a neurologist at London’s National Hospital for Neurology who was not involved in the study. “But we know that there’s an ongoing process.”

Biomarkers are valuable indicators, because they help doctors focus on pathology rather than symptoms. Symptoms can be vague, based on the patient’s subjective experience. They tell you what effect some injury has caused, not what the injury actually is. Biomarkers, however, can be like molecular receipts that point to particular processes, such as axons shearing apart.

When a patient presents with an ambiguous symptom like chest pain, for example, cardiologists can test for biomarkers like troponins and use that information to differentiate between a heart attack or something less severe, like gas or a pulled muscle. “You drill down. You get a specific pathological diagnosis,” says Graham.

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