$1.4 million to investigate how strokes and other events that cut off blood flow to the brain disrupt the blood-brain barrier

The Cleveland Clinic has been awarded a four-year, $1.4 million grant from the National Institutes of Health to investigate how strokes and other events that cut off blood flow to the brain disrupt the blood-brain barrier. Researchers hope to use their findings to develop new methods to limit the damage caused by such events.

The study is being led by Marc Mayberg, M.D., chairman of the Clinic’s Department of Neurosurgery, and Damir Janigro, Ph.D., director of the Cerebrovascular Research Laboratory.

The blood-brain barrier regulates the transport of substances between circulating blood and the brain. It is designed to allow entry into the brain of essential materials, such as nutrients, while keeping out harmful substances.

Researchers, including those at The Cleveland Clinic, already are studying ways to artificially disrupt the blood-brain barrier to allow in substances that otherwise would be kept from reaching the brain, such as chemotherapy drugs for brain cancer patients.

This new research project led by Drs. Mayberg and Janigro will look at ways to prevent barrier disruption rather than cause it. During a stroke, the barrier is compromised by the temporary lack of blood flow. This disruption may be linked to serious neurologic conditions, including additional strokes and hemorrhages.

The study will use a unique laboratory-based model of the blood-brain barrier developed by Dr. Janigro. This model enables researchers to test specific factors that influence the integrity of the blood-brain barrier after stroke by mimicking the events that occur during a stroke. Dr. Mayberg will use the model to study the influence of shear stress (blood flow) on the blood-brain barrier through the release of various mediators known to be involved in inflammatory processes in the body.

“These experiments will help to provide a better understanding of the relationship between microvascular blood flow reductions and the blood-brain barrier,” Dr. Mayberg said. “As a result, these studies may lead to new therapies to reduce the effects of barrier disruption after stroke and in other neurologic disorders. The blood-brain barrier could play a critical role in the treatment of several disorders, including stroke, brain tumors, multiple sclerosis and, potentially, Alzheimer's disease.”