New real-time imaging technique reveals damage from ischemic stroke

Researchers have developed a new, real-time method of imaging the destructive molecular events that occur after an ischemic stroke—a method they hope might one day lead to prevention of the neurovascular damage, according to a study published online ahead of print in the Journal of Cerebral Blood Flow and Metabolism.

“During an ischemic stroke, harmful matrix metalloproteinases—particularly gelatinases—become overactive in areas of the brain where blood flow is cut off,” said the study’s lead author Zezong Gu, PhD, Associate Professor of Pathology and Anatomical Sciences at the University of Missouri School of Medicine, in Columbia, MO. “Overactivation of these enzymes causes brain damage.”

Dr. Gu and his team reasoned that if they could visualize and track gelatinase activity in real time, they could then work on developing a way to block the activity and prevent brain damage from occurring. In this study, they report achieving the first hurdle.

They started with magnetic resonance imaging (MRI) of the brain, which is widely used for stroke diagnosis because of its high-resolution tomographic signal. However, current MRI contrast agents aren’t specific or sensitive enough to provide sufficient contrast enhancement for imaging gelatinase activity.

To overcome this problem, the researchers took a new strategy by using cell-penetrating peptides that specifically recognize gelatinase activity. They tagged these peptides with contrast agents through a process developed by research team member Roger Tsien, PhD, a biochemist and Nobel Laureate at the University of California San Diego School of Medicine, in La Jolla, CA.

“Once the tagged peptides traveled to the site of increased gelatinase activity, they were absorbed into the cells with this activated enzyme,” Dr. Gu said. “When enough of these peptides were absorbed, the stroke site was visible on an MRI.”

The researchers tested this technique in both cell-based and mouse models of ischemic stroke. “Our findings indicate that tagged peptides can be used as a non-invasive probe to detect and track gelatinase activity,” Dr. Gu said. In other words, this imaging could serve as a surrogate indicator of brain damage after stroke.

The researchers are now looking to overcome the second hurdle; they want to find a way to block this gelatinase activity and prevent brain damage from occurring.

“This [imaging] process may serve as an additional tool for clinicians to treat their patients—if a viable inhibitor can be developed to prevent the damage caused by this activity,” Dr. Gu said.

He and his team currently are working to develop such a gelatinase inhibitor.