ISB Researchers Seek a Better Way to Identify Chronic Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) — commonly known as a concussion — has been a frequent injury among U.S. combatants serving in Afghanistan and Iraq, and blast-related mTBI has been called the “signature injury” from nearly two decades of those military conflicts.

Unlike TBI, mTBI can be difficult to diagnose as there often is no observable head injury, even with imaging. Chronic mTBI, where post concussive symptoms persist years after a mTBI event, is very common in veterans who have undergone one or more mTBI event. 

Researchers at Institute for Systems Biology (ISB) in Seattle, led by Principal Scientist Dr. Kai Wang, are working to develop new methods to identify molecular changes in the blood of war veterans diagnosed with chronic mTBI. 

“Diagnostic tools are urgently needed to correctly identify those individuals with chronic mTBI, as this condition can potentially develop into more serious neurodegenerative diseases, such as chronic traumatic encephalopathy (CTE),” said Dr. Vikas Ghai, lead author of a just-published paper in Journal of Neurotrauma.

Ghai and his colleagues from ISB and the Puget Sound VA looked at blood samples from Iraq and Afghanistan war veterans with blast-related mTBI, and compared their findings against samples of a control group that included deployed veterans who have not suffered from mTBI, as well as civilians. 

Researchers examined microRNA (miRNA) in particles called extracellular vesicles, and found they are a great source of the molecular changes and target pathways associated with chronic mTBI. They also found that an enzyme, MME/Neprilysin, is associated with amyloid beta clearance in the brain was elevated in the blood of those suffering from chronic mTBI compared to controls. This is significant because increased brain amyloid beta deposits are pathogenic and found in individuals with mTBI and related neurodegenerative diseases like CTE and Alzheimer’s.

“A growing body of evidence suggests that hidden injuries inside the brain caused by blast-related mTBI may have important differences from repetitive impact mTBI. Nonetheless, we still do not properly understand the nature of these injuries,” said Dr. David Cook of the Veterans Affairs Medical Center and a contributing author on the paper. 

“Thanks to the work of Dr. Ghai and colleagues, new insights into candidate mechanisms of blast-related mTBI have been uncovered,” Cook added. “These findings lend important support for the idea that blast-related mTBI causes chronic changes in how the body’s vascular system works. In addition, this work sets the stage for future studies that will help develop more refined biomarkers of chronic mTBI.”