Newly Identified Stroke Biomarkers Pave Way for Blood Tests to Quickly Diagnose Brain Injuries

Each year, nearly 800,000 individuals in the U.S. experience a stroke, which occurs when blood flow to specific areas of the brain is insufficient, causing brain cells to die due to a lack of oxygen. While magnetic resonance imaging (MRI) is a valuable diagnostic tool for stroke, delays in treatment can lead to worse outcomes. In 2016, the FDA approved a new therapy for tremor disorders, involving high-intensity focused ultrasound (HIFU) to target and destroy a portion of the thalamus, a brain area often responsible for tremors. A recent study has shown that a molecule known as glial fibrillary acidic protein (GFAP) significantly increases in the blood of patients undergoing HIFU treatment for tremors, which causes damage similar to that of a small stroke. This finding, published in Brain Communications, suggests GFAP could be a promising biomarker for stroke and may eventually lead to blood tests for the rapid diagnosis of brain injuries.

In 2022, researchers at UT Southwestern Medical Center (Dallas, TX, USA) reported a technique that improved HIFU targeting for tremor treatment. Recently, the team noticed that the controlled brain injury caused by this therapy appeared similar to a stroke in brain imaging, with both types of damage sharing features, particularly in how the brain responds to these injuries. The researchers hypothesized that this similarity might help achieve the long-sought goal of diagnosing stroke and brain injuries through blood markers. Previous attempts have faced challenges such as a lack of blood samples taken before a stroke, differences in the locations of brain injuries in stroke patients, uncertainty around the timing of strokes, and variations among patients.

The UT Southwestern team believed that using HIFU as a research tool could help overcome these obstacles. In the study, 30 patients with tremor-dominant Parkinson’s disease or essential tremor, another movement disorder, received HIFU treatment. Blood samples were collected before the procedure and at one hour and 48 hours post-treatment. The researchers then measured concentrations of five molecular markers previously identified as potentially useful for diagnosing brain injuries: GFAP, neurofilament light chain, amyloid-beta 40, amyloid-beta 42, and phosphorylated tau 181 (pTau-181). Forty-eight hours following HIFU treatment, all markers except pTau-181 showed significant increases, with GFAP rising the most—more than four times its pre-treatment levels on average.

These results suggest that GFAP could serve as a reliable marker for stroke and other brain injuries. The researchers plan to further investigate GFAP levels at various time points following HIFU treatment to assess its potential as a diagnostic marker for brain injuries. Additionally, they are studying other molecules that might indicate brain injuries even earlier than GFAP. The team has also begun collecting blood from emergency stroke patients to determine whether GFAP levels are elevated in this group.

“This is the first study to use HIFU as a controlled model to evaluate brain injury biomarker dynamics,” said Bhavya R. Shah, M.D., Associate Professor of Radiology and Neurological Surgery at UT Southwestern as well as in the Advanced Imaging Research Center. “The ability to pair a timed pre- and post-HIFU measurement with precise lesion delivery is unprecedented and offers extraordinary potential for validating blood biomarkers of brain injury in a way that has not been done before.”