"Mild Traumatic Brain Injury an Oxymoron:" New Protein Biomarker Highlights Damaged Brain Wiring After Concussion, Finds Penn Study

Physicians and others now recognize that seemingly mild, concussion-type head injuries lead to long-term cognitive impairments surprisingly often. A brain protein called SNTF, which rises in the blood after some concussions, signals the type of brain damage that is thought to be the source of these cognitive impairments, according to a study led by researchers from the Perelman School of Medicine at the University of Pennsylvania, and the University of Glasgow, Glasgow, UK.

“The brain protein specifically indicates the presence of nerve fiber damage that we call diffuse axonal injury,” said senior author Douglas H. Smith, MD, director of the Penn Center for Brain Injury and Repair and the Robert A. Groff Professor of Neurosurgery. “Our findings also confirm that even relatively mild, concussion-type brain impacts can cause permanent damage of this kind.”

The results, published online this week in Acta Neuropathologica, suggest that blood tests for SNTF might one day be used to diagnose diffuse axonal injury and predict cognitive impairment in concussion patients.

A Subtle Form of Damage

Traumatic brain injury (TBI) is the chief cause of death and disability among children and adults from 1 to 44 years of age in the United States, leading to more than two million emergency department visits annually.

“Mild” TBI, or concussion -- often defined as a brief loss of normal brain function typically following a blow to the head -- is by far the most common form of TBI and frequently doesn’t even receive medical attention. Although it is usually make a full recovery, studies in recent years suggest that roughly one in five concussion patients suffers cognitive impairment lasting several months or longer.

The underlying mechanism of this impairment has long been something of a mystery, since concussed brains rarely show signs of bleeding, bruising or other obvious abnormalities on standard CT or MRI scans. However, in severe and fatal TBI cases, direct microscopic examination of the brain often reveals numerous swollen, degenerating, and even fully disconnected axons throughout the white matter -- characteristic of diffuse axonal injury. Many brain injury specialists now suspect that this same type of damage, albeit less extensive, occurs in concussion.

Diffuse axonal injury arises from the sudden movement of the brain in TBI, which rapidly stretches bundles of axons that connect brain regions. Prior research by Smith and others suggests that while affected axons rarely rupture completely at the moment of impact, their sudden deformation causes abnormal inflows of sodium and calcium ions that help regulate a neuron’s function. Investigators surmise that most affected axons manage to pump their sodium and calcium levels back to normal, regain their function, and slowly repair whatever structural damage they have sustained. In other axons, however, levels of calcium become high enough to trigger a self-destruct process, in which protein-breaking enzymes are unleashed, begin to degrade the axonal structure, and ultimately sever the nerve fiber completely.

“Once an axon disconnects and degenerates, it’s never going to regrow to restore that communication pathway across the brain,” Smith said.

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